Ph.D.https://www.autismspeaks.org/taxonomy/term/366/0
en1998 Awards (NAAR) https://www.autismspeaks.org/science/grants-program/research-we-have-funded/1998-awards-naar
<p>In 1998, NAAR committed approximately $500,000 in its second year of funding autism research projects and marked the establishment of NAAR's Mentor-based fellowship program. In 1998, NAAR funded 10 pilot studies and 2 mentor-based fellowships in the United States and Canada. Additionally, NAAR was instrumental in funding and establishing the Autism Tissue Program in 1998, a brain tissue donation program dedicated to autism research. NAAR also attracted its first Research Partners and Research Patrons in 1998, which are listed below.</p><p>David G. Amaral, Ph.D. <br />University of California-Davis, Davis, CA<br /><i>&quot;Magnetic Resonance Imaging &amp; Postmortem Neuroanatomical Evaluation of the Amygdaloid Complex in Autism&quot;</i><br />Two-Year Award: $60,000 <br />Research Partner: Autism Society of Cincinnati</p><p>Charles N. Cartwright, M.D. <br />Mount Sinai School of Medicine, New York, NY <br />NAAR/Bristol-Myers Squibb Research Fellowship in Autism and Neuropharmacology.<br />Two-Year Award: $120,000</p><p>Pam Factor-Litvak, Ph.D.<br />Columbia University School of Health, New York, NY <br /><i>&quot;Autism &amp; Hazardous Waste Sites: An Ecological Study in New Jersey&quot;</i><br />Award Amount: $51,956<br />Research Partner: An Evening At High Point, hosted by Dorothea and Jon Bon Jovi</p><p>Wendy R. Kates, Ph.D. <br />Kennedy Krieger Institute, Baltimore, MD<br /><i>&quot;Neuroanatomic and Neurocognitive Differences Between MZ Twins Discordant for the Narrow Phenotype for Autism&quot;</i><br />Award Amount: $58,546<br />Research Patron: Autism Society of America Foundation</p><p>Yves Lamarre, MD, Ph.D. <br />Center for Research in the Neurological Sciences, University of Montreal, Montreal, Quebec (Canada)<br /><i>&quot;Cerebellar and Cerebral Local Field Potential Oscillations. Relation with Attention and Movement&quot;</i><br />Award Amount: $46,860<br />Research Patron: Audrey Flack and H. Robert Marcus, on behalf of the Autism Society of America Foundation</p><p>Rebecca Landa, Ph.D.<br />The Kennedy-Krieger Institute, Baltimore, MD<br /><i>&quot;Core Deficits of Autism: Evidence from Infant Siblings of Autistic Probands&quot;</i><br />Two Year Award: $60,000<br />Research Partner: Friends and Family of Max LaZebnik Research<br />Patron: Friends and Family of Kayli Phifer (Year 2)</p><p>Rebecca Landa, Ph.D.<br />The Kennedy-Krieger Institute, Baltimore, MD<br />David Zee, MD<br />The Johns Hopkins School of Medicine, Baltimore, MD<br /><i>&quot;The Visual System in Autism: Relations between Oculomotor and Higher Cognitive Functions&quot;</i><br />Two-Year Award: $60,000<br />First Year Research Partner: The Leigh Foundation<br />Second Year Research Partner: Toys R Us</p><p>Anne Messer, Ph.D.<br />Wadsworth Center, New York State Department of Health, Albany, NY<br /><i>&quot;Manipulating the Differentiation and Survival of Cerebellar Purkinje Cells&quot;</i><br />One-Year Award: $29,920</p><p>Katherine D. Tsatsanis, Ph.D.<br />Yale University Child Study Center, New Haven, CT<br />Roland D. Ciaranello, M.D.<br />Memorial Fellowship in Basic Research.<br />Two-Year Award: $100,000</p><p>Christopher A. Walsh, MD, Ph.D<br />Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA<br /><i>&quot;Positional Identification of the Chromosome 15q11-13 Autism Locus&quot;</i><br />Award Amount: $58,872<br />Research Patron: Richard and Susan Smith Family Foundation</p><p>Patricia M. Whitaker-Amitia, Ph.D.<br />State University of New York at Stony Brook<br /><i>&quot;Autoregulation of Serotonin Development&quot;</i><br />Award Amount: $60,000<br />Research Patron: Norma and Malcolm Baker</p><p>Andrew W. Zimmerman, MD<br />Kennedy Krieger Institute, Baltimore, MD<br /><i>&quot;The Role of Neural Cell Adhesion Molecule in Autism&quot;</i><br />Award Amount: $30,000<br />Research Partner: Solving the Mystery of Autism Foundation, Inc.</p>ScienceAlbanyAnne MesserAudrey Flack and H. Robert MarcusAutism Society of America FoundationBaltimoreBeth Israel Deaconess Medical Center/Harvard MedicalCACenter for Research in the Neurological SciencesCharles N. CartwrightChristopher A. WalshColumbia University School of HealthCTDavid G. AmaralDavid ZeeDavisKatherine D. TsatsanisKennedy Krieger InstituteMontrealMount Sinai School of MedicineNew HavenNew YorkNew York State Department of HealthNYon behalf of the Autism Society of America FoundationPam Factor-LitvakPh.DPh.D.Quebec (Canada)Rebecca LandaRoland D. CiaranelloThe Johns Hopkins School of MedicineThe Kennedy-Krieger InstituteUniversity of California-DavisUniversity of MontrealWadsworth CenterWendy R. KatesYale University Child Study CenterYves LamarreGrantsGrantsFri, 06 May 2011 02:11:15 +0000pwhalen@gmail.com455 at https://www.autismspeaks.org1998 Grants Funded (CAN) https://www.autismspeaks.org/1998-grants-funded-can
Search for a candidate gene in autism
<p><strong>Julia Bailey, Ph.D., University of California, Los Angeles (Young Investigator)</strong><br />The goal of this project is to identify associations of candidate genes and autistic disorder through a family based non-parametric (model free) method. This method does not require assumptions about the disease process and focuses on regions that have been previously identified in literature, through chromosomal aberrations, or in association with other disorders. Once susceptibility genes can be identified and mapped, it will allow for more accurate and earlier diagnoses and better treatment through target gene therapy.</p>
Quantitative neuroanatomical correlates of cognitive dysfunction in autism
<p><strong>James E. Black, M.D., Ph.D, University of Illinois at Urbana-Champaign (Pilot Research)</strong><br />Alterations of the connections between neurons are thought by some to be the basis for behavior and intellectual problems of autism. This study will utilize new microscopy techniques to examine neuronal connections in areas of the brain that, according to recent studies, have substantial differences in volume and have been pinpointed as most likely to have pathological organization. Specific focus will be on the examination of neuron fibers connecting the cerebral hemispheres (measures that presumably would reflect disturbed cortical development), neurons in the anterior cingulate cortex (areas involved in regulating attention and higher cognitive functions) and neurons in the cerebellum (another area strongly implicated in the psychopathology of autism)</p>
Serotonin transporter gene and autism
<p><strong>Randy D. Blakely, Ph.D., Vanderbilt University (Pilot Research)</strong><br />This study seeks to determine whether forms of a gene that controls the availability of the brain chemical serotonin - a chemical that has been implicated in many mood and thought disturbances - is specifically inherited in autism and whether subgroups can be identified genetically. Findings may ultimately help identify at risk children and establish better guidelines for rational drug treatments.</p>
The genetics of autism - Screening the human genome for linked markers in autism
<p><strong>Joseph D. Buxbaum, Ph.D., Mount Sinai (Pilot Research)</strong><br />Diseases with genetic components are associated with alterations in genes which are heritable. This study focuses on the genetic contribution to autism by screening the human genome for markers which are close to altered genes. Such analysis is intended to lead to the identification of regions of the genome which contain genes causative in the development of autism and ultimately the responsible genes themselves. Novel therapies based on these genes can then be developed.</p>
D8/17 positivity in autism: Implications for etiology, subtyping and treatment
<p><strong>Gina DelGiudice-Asch, M.D., Mount Sinai (Pilot Research)</strong><br />Recently, the monoclonal antibody D8/17 marker has been found to be elevated in a subtype of obsessive-compulsive disorder subjects. It has also served as a marker for genetic susceptibility to rheumatic fever which is produced by an autoimmune response to streptococcal antigens, some of which are described by obsessive compulsive symptoms and accompanying movement disorders. This study will assess D8/17 in matched autism and control subjects, assess antineuronal antibodies, and explore the role of D8/17 in the cause, expression and treatment of autism.</p>
Autism: Brain morphometry and cognitive neuroscience
<p><strong>Martha R. Herbert, M.D., Ph.D., Massachusetts General Hospital (Young Investigator)</strong><br />Existing evidence such as abnormal brain size and thinking processes in autistic children suggests that the whole brain is affected in autism. Up until now, techniques for studying brain structure abnormalities have looked only to specific areas of the brain. In this study, the whole-brain structure analysis method (which analyzes the whole brain into fine-grained units so that volumes for every part and region of the brain can be determined) will be applied to autism for the first time. The purpose of this analysis is to provide new ways of understanding where the abnormalities are distributed in the autistic brain and what went wrong in the brain's development to make it this way.</p>
Fluoxetine/placebo treatment of childhood/adolescent autism: Clinical predictors and dimensional severity
<p><strong>Eric Hollander, M.D., Mount Sinai (Pilot Research)</strong><br />Using a sixteen week placebo-controlled trial, this study will assess the effects of fluoxetine (a serotonin reuptake inhibitor medication commonly known as Prozac) in children and adolescents on overall autistic severity and compulsive, language and social deficit dimension found in autism.</p>
Auditory information processing in autism
<p><strong>Jeff Lewine, Ph.D., University of Utah (Pilot Research)</strong><br />This study will use a new brain imaging technique called Magnetic Source Imaging (MSI) to evaluate auditory processing and brain organization before and after Auditory Integration Training (AIT), a therapy involving listening to frequency and amplitude modulated music. It is hypothesized that autistic children show unusual auditory profiles because of disorganization of the mapping of the auditory signal space onto the brain surface and that AIT stimulates the brain, producing a reorganization of auditory processing. Using MSI it is possible to determine exactly which parts of the brain process specific sounds. This study will ultimately help to clarify the baseline auditory dysfunction in autistic children, define the mode of action for AIT and determine its clinical efficacy.</p>
Post-mortem evaluation of the amygdaloid complex in autism
<p><strong>Margherita Molnar, University of California, Davis (Young Investigator)<br /></strong>Abnormalities in the amygdala are thought among researchers who study behavior in autism to underlie the social and emotional abnormalities in this disorder. In order to identify neural and molecular abnormalities in the amygdala in patients with autism, this project will utilize standard anatomical and histological procedures, and more advanced sterological and molecular techniques to perform postmortem neuroanatomical studies on the amygdaloid complex in a small sample of autistic cases and matched controls. In addition, utilizing immunohistochemical techniques, the expression of certain critical neurotransmitters will be analyzed.</p>
Biochemistry of nucleotidase-associated pervasive developmental disorder (NAPDD)
<p><strong>Theodore Page, Ph.D., University of California, San Diego (Pilot Research)</strong><br />The goal of this project is to develop a rapid screening method for Nucleotidase-Associated Pervasive Developmental Disorder (NAPDD), a seemingly common autistic syndrome characterized by poor social interaction, hyperactivity, distractibility, speech deficit, seizures, ataxia and frequent infections. Focus will also be on determining how the biological defect in this disorder causes autistic symptoms, and the basis of the effectiveness of uridine in the treatment of this disorder. This will lead not only to a better understanding of NAPDD but of autistic disorders in general.</p>
Neuropathology of cerebral cholinergic activities in autism
<p><strong>Elaine Perry, Ph.D., University of Newcastle (England) (Pilot Research)</strong><br />This study is based on the idea that one of the disturbances in brain transmitter signaling systems in autism involves a chemical called acetylcholine. The acetylcholine system is critically involved in attentional processes, an area clearly affected in autism. In examining a range of molecular markers in adult brain tissue, researchers will determine if and how the acetylcholine system is directly involved. Results from this study could lead to new testing of drugs aimed at restoring normal system functioning. <strong>First year funding partner: Solving the Mystery of Autism Foundation, Inc.</strong></p>
Randomized, double-blind, placebo controlled parallel antibiotic trial for the treatment of late onset autism
<p><strong>Richard H. Sandler, M.D., Rush Presbyterian-St. Luke's Medical Center (Pilot Research)</strong><br />This trial will be conducted on a subgroup of autistic children with chronic diarrhea and delayed onset autism. As many of this group have frequent antibiotic courses preceding their chronic diarrhea, this study will explore the possible role of antibiotics in releasing neurotoxins that are thought to be present in the system and that might be implicated in autism.</p>
The role of the frontal cortex and the amygdala in the social deficits in autism
<p><strong>Valerie Stone, Ph.D., University of Cambridge (Young Investigator)</strong><br />The goal of this study is to develop an instrument/test that measures different levels of social skills, from non-verbal to verbal. This test is being used to compare individuals with autism or Asperger's Syndrome and neurological patients whose social deficits mirror those of people with autism. In the future, it is hoped that these social tests can be used in neuroimaging research in which the brain activation of normal individuals is scanned while they are using specific social skills. Understanding which neural structures are involved in social abilities will allow for the design of more appropriate interventions and new treatments for individuals with autism.</p>
ScienceDavisElaine PerryEric HollanderGina DelGiudice-AschJames E. BlackJeff LewineJoseph D. BuxbaumJulia BaileyLos AngelesMargherita MolnarMartha R. HerbertMassachusetts General HospitalMount SinaiPh.DPh.D.Randy D. BlakelyRichard H. SandlerRush Presbyterian-St. Luke's Medical CenterSan DiegoTheodore PageUniversity of CaliforniaUniversity of CambridgeUniversity of Illinois at Urbana-ChampaignUniversity of NewcastleUniversity of UtahValerie StoneVanderbilt UniversityGrantsGrantsFri, 06 May 2011 02:05:17 +0000pwhalen@gmail.com454 at https://www.autismspeaks.org1999 Awards (NAAR) https://www.autismspeaks.org/science/grants-program/research-we-have-funded/1999-awards-naar
<p>The 1999 Research Awards marked the third year NAAR funded autism research programs and the first time the organization had funded autism research in Europe. NAAR invested $800,000 in 1999 to fund 14 pilot studies and two mentor-based fellowships in the United States, Russia and Italy.</p><p>Pavel Belichenko, M.D., Ph.D.<br />Russian Academy of Medical Sciences, Moscow, Russia<br /><i>&quot;The Role of the Brain-Directed Autoimmune Reaction in the Pathogenesis of Infantile Autism in Children and Young Adults&quot;.</i><br />One-Year Award: $30,000<br />Research Partner: Solving the Mystery of Autism Foundation, Inc.</p><p>David R. Cool, Ph.D. <br />Wright State University, Dayton, OH<br /><i>&quot;Neuro-Endocrine Peptide Hormones are Implicated in Social Behavior Development: Oxytocin Involvement in Autism&quot;.</i><br />Two-Year Award: $60,000<br />Research Partner: Autism Society of Cincinnati<br />Research Partner: Solving the Mystery of Autism Foundation</p><p>Guinevere Eden, D.Phil. <br />Georgetown University Institute for Cognitive and Computational Sciences, Washington, D.C.<br /><i>&quot;Functional Neuroanatomy of Reading in Hyperlexic Children Studied with Functional Magnetic Resonance Imaging&quot;.</i><br />Two-Year Award: $59,989<br />Research Partner: Autism Coalition for Research &amp; Education</p><p>Robert Holson, Ph.D.<br />New Mexico Tech, Socorro, NM<br /><i>&quot;Gestational Retinoic Acid Exposure: An Animal Model of Autism&quot;.</i><br />One-Year Award: $29,480</p><p>Flavio Keller, M.D.<br />Libera Universita, Campus Bio-Medico (Rome, Italy)<br /><i>&quot;Characterization of the Serotonin Blood Levels and of the Serotonin Uptake Stimulating Peptides in Plasma of Normal Subjects and Autistic Patients&quot;.</i><br />One-Year Award: $19,492</p><p>Anne Messer, Ph.D.<br />Wadsworth Center, New York, State Department of Health, Albany, NY<br /><i>&quot;Manipulating the Differentiation of Survival of Cerebellar Purkinje Cells&quot;.</i><br />One-Year Award: $30,000 (continuation grant)<br />Research Partner: Madeline &amp; Arthur Millman, on behalf of the Autism Society of America Foundation</p><p>Judith Miles, M.D., Ph.D.<br />University of Missouri, Columbia, MO<br /><i>&quot;Identification of Dysmorphology Based Autism Groups&quot;.</i><br />Two-Year Award: $60,000</p><p>Timothy P.L. Roberts, Ph.D.<br />University of California-San Francisco, San Francisco, CA<br /><i>&quot;Cortical Processing of Complex Sounds: Implications for Language Impairment in the Autistic Brain&quot;.</i><br />Two-Year Award: $57,852<br />Research Partner: Autism Coalition for Research &amp; Education<br />Research Partner: Toys R Us, Inc.</p><p>Donald C. Rojas, Ph.D.<br />University of Colorado, Boulder, CO<br /><i>&quot;Anatomical and Functional Development of the Auditory Cortex in Children with Autism&quot;.</i><br />Two-Year Award: $56,603 Research Partner: New Orleans Friends of NAAR</p><p>Gleb P. Shumyatsky, Ph.D.<br />Columbia University, New York NY<br /><i>&quot;A Genetic Analysis of the Role of the Amygdala in Autistic Behavior using Genetically Modified Mice&quot;.</i><br />Two-Year Award: $59,882<br />Research Partners: Mellanby Family &amp; Autism Society of Broward County</p><p>Moyra Smith, M.D., Ph.D.<br />University of California-Irvine, Irvine, CA<br /><i>&quot;Analysis of Chromosome 15q22 Deletion Associated with Autism and Immune Deficiency&quot;.</i><br />One-Year Award: $30,000</p><p>Wayne L. Strauss, M.D., Ph.D.<br />University of Washington, Seattle, WA<br />NAAR/Bristol-Myers Squibb Research Fellowship in Autism and Neuropharmacology.<br />One-Year Award: $60,000</p><p>Christopher J. Stodgell, Ph.D.<br />University of Rochester, Rochester, NY<br />Roland D. Ciaranello, M.D. Memorial Fellowship in Basic Research.<br />Two-Year Award: $100,000</p><p>Karen M. Weidenheim, M.D.<br />Albert Einstein College of Medicine, New York, NY<br /><i>&quot;Role of Connectivity in Autism&quot;.</i><br />Two-Year Award: $59,840<br />Research Partner: The Mellanby Family &amp; Autism Society of Broward County</p><p>John P. Welsh, Ph.D. New York University School of Medicine, New York, NY<br /><i>&quot;Functional Analysis of Rodent Autism Model&quot;.</i><br />Two-Year Award: $60,000</p><p>James T. Winslow, Ph.D. Emory University, Atlanta, GA<br /><i>&quot;Characterization of the Social Behavior of Inbred Mouse Strains&quot;.</i><br />One-Year Award: $30,000ScienceAlbanyAlbert Einstein College of MedicineAnne MesserAtlantaCampus Bio-Medico (RomeChristopher J. StodgellColumbia UniversityColumbiaTimothy P.L. RobertsD.Phil.David R. CoolDonald C. RojasFlavio KellerGAGeorgetown University Institute for Cognitive and Computational SciencesGleb P. ShumyatskyGuinevere EdenItalyJames T. WinslowJohn P. WelshJudith MilesKaren M. WeidenheimLibera UniversitaMoscowMoyra SmithNew Mexico TechNew YorkNYPavel BelichenkoPh.D.Ph.D. Emory UniversityPh.D. New York University School of MedicineRobert HolsonRussian Academy of Medical SciencesState Department of HealthUniversity of California-IrvineUniversity of California-San FranciscoUniversity of ColoradoUniversity of MissouriUniversity of RochesterUniversity of WashingtonWadsworth CenterWayne L. StraussWright State UniversityGrantsGrantsFri, 06 May 2011 01:46:06 +0000pwhalen@gmail.com452 at https://www.autismspeaks.org1999 Grants Funded (CAN) https://www.autismspeaks.org/science/grants-program/research-we-have-funded/1999-grants-funded-can
Search for susceptibility genes in autism
<p><strong>Catalina Betancur, M.D., Ph.D., INSERM France (Young Investigator)</strong><br />Recently an international collaborative project, the Paris Autism Research International Sib-pair (PARIS) study, performed a genome-wide screen for susceptibility genes in 51 multiplex pedigrees affected with autism. Among the 12 potential chromosomal regions identified, five overlapped with results of other recent studies. This project will focus on these five regions in the sib-pair population and in an additional population of trios (affected child and both parents) in order to lead to greater understanding of the etiology and pathogenesis of autistic disorders. First year funding partner: Eugene and Sherna Schloss in honor of their grandson, Samuel Mathias Schloss</p>
Protein glycosylation and autistic spectrum disorders
<p><strong>Hudson H. Freeze, Ph.D., The Burnham Institute (Pilot Research)</strong><br />Glycosylation (the process of adding sugar chains to proteins) occurs in all proteins in the blood and many in the cell membranes. Much of the cell-cell communication during embryonic development also involves glycosylation. As a result, it has many roles in the body including control of how proteins fold into their active shapes or their delivery to the proper location inside the cell, and movement of white blood cells during infections or inflammation. This means that the loss of a sugar chain or construction of an incomplete sugar chain can have many serious consequences. Several patients with an unknown glycosylation defect have show to have an autistic-like presentation. This study with focus on locating their defect as well as screening multiplex families for signs of altered glycosylation.</p>
A murine model system to study autism
<p><strong>Daniel Goldowitz, Ph.D., University of Tennessee, Memphis (Pilot Research)</strong><br />Using a neurogentic mouse model of autism that is being developed, this project will combine experimental embryological, behavioral and anatomical techniques to explore the role of perturbations of the cerebellum in the onset of behaviors that mimic autism. This model can then be used to test interventions during development aimed at improving and eliminating behavioral deficits.</p>
A genetic analysis of the role of the amygdala in an animal model of autistic behavior
<p><strong>Eric R. Kandel, M.D., Columbia University (Bridge Grant)</strong><br />This group is interested in developing an animal model for components of autism. Accumulated evidence from previous studies suggests that emotional state in autistic patients, disorders of anxiety and depression, and experimental models like Kluver-Bucy syndrome have in common one structure in the brain, namely the amygdala, which deals with unconscious memories of emotions and fear. Therefore the localization, cloning and further characterization of the genetic substrates underlying amygdala function and its relationship to autistic behavior will allow for a detailed molecular analysis of the anatomical and signaling pathways that contribute to the clinical syndrome.</p>
Expression analysis of genes in 15q11-13: Identification of autism candidate genes
<p><strong>Laura B. Kubicek Herzing, Ph.D., University of Chicago (Young Investigator)<br /></strong>Human chromosome 15 (15q11-13) contains hotspots for chromosomal rearrangements, flanking a variety of genes involved in brain development and function. These include candidate loci for schizophrenia (CHRNa7) and Angelman Syndrome (UBE3A), as well as GABA, receptor subunit genes. UBE3A is, in mice, imprinted in regions of the brain which may show abnormalities in autism, and transgenic mice deleted for GABRB3 demonstrate potential autistic features. Intriguingly, maternal inheritance of a duplicated 15q11-13 region is associated with autism, and autism/PDD/atypical AS are also observed with presence of a supernumerary marker chromosome derived from this region. In addition, linkage to 15q11-13 has recently been detected in non-dup(15) autism patients. Together, these observations strongly suggest 15q11-13 contains an autism gene(s). The primary ways in which alteration of gene/region copy number could influence phenotype involve changes in gene expression levels. To analyze gene expression across 15q11-13, and to determine a possible correlation between gene expression patterns and autism, I will utilize Reverse-Transcriptase-Polymerase-Chain-Reaction and RNA-Fluorescence In-Situ Hybridization. The imprint status will be determined for genes across the region, primarily in the brain; maternal-specific expression could explain the correlation between maternal inheritance of dup(15) and disease phenotype. Expression levels of genes between dup(15) (autism), marker(15), karyotypically normal autistic patients and normal controls will be compared to determine over/under expression of gene clusters/chromosome regions and individuals genes. This data will help identify candidate genes for autism, provide valuable information for other neurobiological genes in the region, and may be instrumental in determining a mechanism for the dup(15) phenotype.</p>
The effects of pharmacological deactivation of the amygdala on social behavior in nonhuman primates
<p><strong>Ludise Malkova, Ph.D., Georgetown University Medical Center (Pilot Research)</strong><br />A primary symptom of autism is impairment in social relations. This impairment together with mental retardation suggests, based on human cases and experiments in nonhuman primates, that dysfunction in medial temporal lobes might be involved in the etiology of this developmental disorder. Our previous studies have shown that early damage to the medial temporal lobes (including the amygdala) in monkeys resulted in severe and long-lasting socioemotional disturbances, such as the dramatically reduced social contact and increased self-directed activities, strikingly similar to those seen in autistic children. These disturbances were more severe than those after the same lesions inflicted by the same lesions in adulthood and were related more specifically to the amygdala. Here, we are proposing an alternative approach to lesion studies, a transient pharmacological inactivation of the amygdala to more precisely investigate the neural substrates of social interactions in infant monkeys. Focal infusions of drugs that block glutamate transmission will be aimed at particular subdivisions of the amygdala in freely moving, nonsedated monkeys and the effects of these drugs on social interactions in monkeys observed in pairs (as differentiated from nonsocial cognitive task performance) will be assessed. If our aims are achieved, it will allow us to embark in the future on studies to evaluate the developmental impact of focal drug application in the monkey; an important goal will be to determine of a repeated blockage of the transmission in the amygdala over a critical period of the monkeys' developmental results in long-lasting consequences for its socioemotional behavior.</p>
Stimulating social communication and affective expression in autistic children: A neurophysiological approach
<p><strong>Stephen W. Porges, Ph.D., University of Maryland (Pilot Research)</strong><br />This study hypothesizes that social interaction and communication problems for many autistic children are, in part, caused by functional problems and not irreversible structural problems in the nervous system. Thus, to promote more appropriate social behavior, an intervention has been designed which attempts to stimulate and exercise the cortical regulation of the nerves that control the muscles in the head through computer-altered acoustic stimulation delivered via earphones in a quiet, supportive environment. Preliminary results show positive improvements immediately following intervention and persisting during a three month follow-up.</p>
Early diagnosis of autistic regression
<p><strong>Isabelle Rapin, M.D., Albert Einstein College of Medicine (Pilot Research)</strong><br />Studies show that a great majority of toddlers who undergo a language regression develop autistic behaviors that usually persist. In fact, language/behavioral regression is reported by at least a third of parents of children on the autistic spectrum. The cause of the regression is unknown because children are rarely referred at the time of the regression. The purpose of this study is to determine whether subclinical epilepsy (which is diagnosed when a prolonged sleep EEG shows epileptiform activity even though the child has no known seizures) plays a role in early language regression. Progress of children who receive medication will be compared with those who do not but, like the others, are receiving speech/language therapy and special education at home or in school. Children will be followed at three and six months to determine the course of their language and behavioral deficits. Pilot data provided by this study will be used as the basis for submission of an NIH grant for a large 4 arm multi-institutional double blind treatment trial.</p>
Role of the prefrontal cortex in auditory and visual cognitive function relevant to autism
<p><strong>Lizabeth M. Romanski, Ph.D., Yale University (Young Investigator)</strong><br />Research has shown that the ventrolateral frontal lobe is involved in both face perception and the processing of language related sounds. This convergence of face and language information on a single region of the frontal lobe suggests that this brain region may be important for memory, communication and social interaction, and thus may be particularly affected by autism. This project is aimed at further understanding how the neurons and brain circuits in this region normally participate in face and language processing. This may help to develop better and earlier diagnostic tests and design targeted treatments aimed at improving language and social capabilities in children with autism.</p>
An investigation into sleep disorders in children with autism
<p><strong>Richard Shubin, M.D., Huntington Memorial Hospital (Bridge Grant)</strong><br />Although parents of children with autism have long known that their children have significant problems with sleep, there is a dearth of scientific and medical literature on the impact of sleep disorders on the lives of these children. A systematic effort to improve nighttime sleep by diagnosing and treating sleep disorders could enhance the ability of the child to function during the day. We will study sleep in autistic children using polysomnography in a clinical context.</p>
ScienceAlbert Einstein College of MedicineCatalina BetancurColumbia UniversityDaniel GoldowitzEric R. KandelGeorgetown University Medical CenterHudson H. FreezeHuntington Memorial HospitalINSERM FranceIsabelle RapinLaura B. Kubicek HerzingLizabeth M. RomanskiLudise MalkovaMemphisPh.D.Richard ShubinStephen W. PorgesThe Burnham InstituteUniversity of ChicagoUniversity of MarylandUniversity of TennesseeYale UniversityGrantsGrantsFri, 06 May 2011 01:36:38 +0000pwhalen@gmail.com451 at https://www.autismspeaks.org2000 Awards (NAAR) https://www.autismspeaks.org/science/grants-program/research-we-have-funded/2000-awards-naar
<p>In 2000, NAAR became the first non-governmental organization to break the $1 million mark for funding autism research and committed approximately $1.5 million to fund 19 pilot studies and two mentor-based fellowships in autism research taking place in the United States and Spain. Also in 2000, NAAR and the Nancy Lurie Marks Family Foundation began sponsoring the Autism Genetics Cooperative, an annual retreat for an international consortium of the world's leading genetic researchers focusing on autism to share information and combine data to accelerate the search for autism susceptibility genes.</p><p><b>
<b>David G. Amaral, Ph.D.<br />University of California-Davis, Davis, CA</b>
</b><br /><i>&quot;Postmortem Neuroanatomical Evaluation of the Amygdaloid Complex in Autism&quot;</i><br />Two-Year Award: $68,000<br />Research Partner: Autism Society Cincinnati</p><blockquote><p>Infantile autism is a neurobiological disorder that severely disrupts social, cognitive, and language development. While studies have hinted that alterations in the section of the brain called the &quot;amygdala&quot; underlies the social and emotional abnormalities in autism, a complete analysis is long overdue. This study, under the direction of Dr. David Amaral, will evaluate this hypothesis with a complete quantitative analysis of the atypical neural organization in individuals with autism. Using brain samples provided by the Autism Tissue Program, his group will actually count the number of neurons in each subdivision of the amygdala, comparing sizes and shapes. They will then extend their analysis to determine subtler neurochemical abnormalities. If a relationship is confirmed, changes in the structure of the amygdala may prove to be a useful in the diagnosis of autism using safe noninvasive imaging techniques.</p></blockquote><p><b>
<b>Gene J. Blatt, Ph.D.<br />Boston University Medical School, Boston, MA</b>
</b><br /><i>&quot;Cerebellar Circuitry in Autism&quot;.</i><br />Two-Year Award: $94,878<br />Research Partner: Nancy Lurie Marks Family Foundation</p><blockquote><p>Previous studies have indicated that in part of the brain called the &quot;posterolateral cerebellar cortex&quot;, there is a reduction in number of a specific type of cells called &quot;purkinge&quot; in individuals with autism. The missing cells raise interesting questions such as: Were the purkinge cells ever produced? Is it a specific type of purkinge cell that is affected? What happens to the typical connections purkinge cells make with other brain cells? Studying the circuitry of the purkinge cells may allow researchers to understand the developmental timing of autism, and understand the areas susceptible to intervention. Dr. Blatt and his colleagues intend to evaluate the changes in the integrity of autistic purkinge cells and determine any morphological differences. A part of the brain called the &quot;inferior olivary nucleus&quot; will also be evaluated, as it normally sends projections to the purkinge cells. Studies will be performed through histochemical methods to illuminate the specific properties of the purkinge cells.</p></blockquote><p><b>
<b>Ira L. Cohen, Ph.D.<br />New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY</b>
</b><br /><i>&quot;Epidemiology of Autism on Staten Island&quot;.</i><br />Two-year Award: $79,504</p><blockquote><p>Although the causes of autism are unknown, there has been a heightened concern among parent groups, the media, and medical professionals about exposure to environmental toxins. Dr. Ira L.Cohen and his colleagues will shed light on the impact of environmental factors by investigating a disproportionately high incidence of autistic individuals in the Staten Island area, where there is a large number of toxic waste sites situated within a small geographical region. Population data will be used to identify two hundred children with autism between the ages of 6-12. Through diagnostic tools (ADI and ADOS-G), these previously reported cases of autism will be reevaluated to ensure a correct initial diagnosis. This study has direct relevance to previous studies, such as the evaluation of Brick Township N.J., where a disproportionately high incidence of autistic individuals was reported.</p></blockquote><p><b>
<b>John N. Constantino, M.D. <br />Washington University School of Medicine, St. Louis, MO</b>
</b><br /><i>&quot;A Quantitative Genetic Measure of Autistic Traits&quot;.</i><br />Two-Year Award: $58,762<br />Research Partner: Autism Coalition for Research &amp; Education</p><blockquote><p>Currently diagnostic measures of autistic spectrum deficits focus on establishing a definitive diagnosis of autism. However, clinical studies have suggested that autistic disorder represent the upper extreme of quantitative traits that are variably distributed in the population.</p><p>Dr. John N. Constantino and his collegues have developed the Social Reciprocity Scale (SRS) that was designed to ascertain autistic symptoms across the entire spectrum of the autistic disorder, from unaffected to the severely affected. In this study, the SRS was validated by strict comparisons with the Autism Diagnostic Interview-Revised (ADI-R), the only diagnostic tool for autism spectrum disorders which has been standardized, rigorously tested and universally recognized as a &quot;gold standard&quot; for supporting the diagnosis of autistic disorder. The SRS could feasibly be used to study the genetics of autism in whole populations, given its ease of administration and its known psychometric properties in epidemiologic samples of children. It takes only 15-20 minutes to complete and can be done so by parents and/or teachers. The SRS may have very important clinical utility in quantifying and characterizing autistic spectrum traits, which are sub threshold for the full diagnosis of autism and be useful for monitoring the effects of treatment of autistic spectrum disorders.</p></blockquote><p><b>
<b>Deborah A. Fein, Ph.D.<br />University of Connecticut, Storrs, CT</b>
</b><br /><i>&quot;Early Detection of Pervasive Developmental Disorders&quot;</i><br />Two-Year Award: $70,658<br />Research Partner: Autism Society of America Foundation Morton</p><blockquote><p>With currently available diagnostic instruments, autism is difficult to detect in very young children. The average age at which parents express first concern to their pediatrician is 17 months, but the average age of diagnosis is 4 years. Since there is evidence exists that early detection and intervention can lead to substantially better prognosis, this is clearly an issue. The first diagnostic tool specifically designed to screen for autism was the British Checklist for Autism in Toddlers (CHAT), designed for 18 month old children. Despite the major advance represented by the development of the CHAT, several modifications to its&#213; structure were considered advantageous for further development of this early screening technology.</p><p>Dr. Deborah Fein and her colleagues have addressed the limitations and shortfall of the CHAT and developed a comprehensive version referred to as the M-CHAT (Modified Checklist for Autism in Toddlers). This study involves the validation of this new widely usable, screening tool for autism, which assesses 23 items in a checklist format to use at the child&#213;s 24 month checkup to determine cognitive, language, and adaptive functioning. Furthermore, the study will investigate parameters of more successful treatment programs for young children with autism.</p></blockquote><p><b>
<b>Ann Gernsbacher, Ph.D. &amp; H. Hill Goldsmith, Ph.D.<br />University of Wisconsin, Madison, WI</b>
</b><br /><i>&quot;Toward a Dyspraxic Subtype of Autistic Spectrum Disorder&quot;.</i><br />Two-Year Award: $96,571<br />Research Partner: Nancy Lurie Marks Family Foundation</p><blockquote><p>Even when diagnosed according to strict and consistent criteria, symptom profiles of persons with autism vary greatly, suggesting that the cause of autism has many origins. Therefore there is value in identifying possible subtypes of autism and to focus research on these subtypes.</p><p>Dr. Ann Gernsbacher is interested in investigating developmental verbal dyspraxia (DVD), a disorder resulting in difficulty coordinating and sequencing the oral-motor movements necessary to produce and combine speech sounds, and a common affliction in autistic individuals. For this project, she and her collegues will identify and validate a DVD subtype of autism by screening all children with autism (under age 18) in a metropolitan area. They will collect extensive behavioral, medical, and developmental histories of all the children, obtain neuroanatomical (structural MRI) data; and collect DNA for future candidate gene studies. Indices of the DVD subtype will be constructed using current diagnostic tools (e.g., the ADI and A-DOS).</p></blockquote><p><b>
<b>Scott E. Hemby, Ph.D.<br />Emory University, Atlanta, GA</b>
</b><br /><i>&quot;Gene Expression Profiling of Autism: Alterations in Temporal Lobe Profiles&quot;.</i><br />Two-Year Award: $70,658<br />Research Partner: Madeline &amp; Arthur Millman, on behalf of the Autism Society of America Foundation</p><blockquote><p>Despite considerable research effort over the past several decades, identifying the neuropathology underlying the behavioral abnormalities related to autism remains elusive. It is feasible that the changes in brain function are subtle and correspond to alterations at the molecular level in discrete brain regions, or even in specific brain cells, leading to pronounced changes in brain function.</p><p>Several studies indicate dysfunction of the temporal lobe of the brain in autism, specifically, the hippocampal formation and entorhinal cortex. Under the supervision of Dr. Scott E. Hembel, this study will assess alterations in gene expression in these areas of the brain using rhesus monkeys and post-mortem tissue from autistic individuals. Rhesus monkeys serve as good models to study autism, as they can produce associated behaviors when introduced into social groups, such as, social withdrawal and repetitive and stereotypic behaviors. The proposed experiments will utilize state of the art molecular biology procedures, including cDNA microarrays, to assess regional and single cell gene expression and provide information thus far unattainable. Identification of altered expression of multiple genes should establish a &quot;fingerprint&quot; of the molecular changes in autism and provide new targets for interventions.</p></blockquote><p><b>
<b>Cynthia R. Johnson, Ph.D.<br />University of Pittsburgh, Pittsburgh, PA</b>
</b><br /><i>&quot;Assessment and Treatment of the Cognitive Basis of Behavioral Impairments in Autism&quot;.</i><br />Two-Year Award: $40,218<br />Research Partner: Pittsburgh Friends of NAAR</p><blockquote><p>Individuals with autism very frequently experience challenging behaviors that greatly interfere with optimal learning. Furthermore, behavior impairment such as aggression, self-injury, and disruption very often result in more restricted educational settings. While the accumulated behavioral research on assessment and treatment has been of value, the recognition of the cognitive underpinnings of problematic behaviors in autism has been virtually ignored.</p><p>Dr. Cynthia R. Johnson and her colleagues will examine several cognitive factors and relate these factors to behavioral impairments in high functioning autistic and Aspergers adolescents with verbal and full scale IQs of 80 or greater. The elucidation of these likely complex relationships has significant implications for advancing our understanding of the neurobiological mechanism driving behaviors. This study will also apply cognitive mediated treatment procedures focusing on skills such as problem solving, time management, planning and flexibility. If successful, this treatment will aid in the improvement of school performance by attenuating the display of problematic interfering behaviors and serve as a guide for development of future treatments that can intervene earlier and more effectively.</p></blockquote><p><b>
<b>William G. Johnson, M.D.<br />UMDNJ&#8211;Robert Wood Johnson Medical School (New Brunswick, NJ)</b>
</b><br /><i>&quot;MHC Extended Haplotypes as Risk Factors for Autism&quot;.</i><br />Two-Year Award: $80,000<br />Research Partner: Doug Flutie, Jr. Foundation for Autism, Inc.</p><blockquote><p>A group of genes called the major histocompatibility complex (MHC) located on chromosome 6 is a major risk factor for autoimmune diseases. There is evidence that the MHC is also a risk factor for autism. In fact, it has been suggested that certain clusters of MHC genes called &quot;extended haplotypes&quot;, give the highest relative risk of any genetic risk factor for autism yet identified. Unfortunately, this information comes from a study design (allelic association) that can give false positive results.</p><p>Using a robust study design called &quot;transmission disequilibrium&quot;, Dr. William G. Johnson and his colleagues intend to resolve this issue and determine the frequency of autoimmune disorders in individuals with autism and their family members. In this method, the transmission frequencies of traits from parent to child are compared with those expected by chance. The use of internal controls avoids the problem of population stratification. Using this same technique, Dr. Johnson's group has recently shown an increased frequency of autoimmune diseases and other developmental disorders in individuals with spina bifida. The current study will provide insight into the mechanism by which autoimmune disorders are risk factors for autism and test the hypotheses that certain MHC extended haplotypes are risk factors for autism that act indirectly through mothers during pregnancy.</p></blockquote><p><b>
<b>Ami Klin, Ph.D.<br />Yale University Child Study Center, New Haven, CT</b>
</b><br /><i>&quot;Visual Scanning Patterns and Mental Representations of Social Interaction in Infants and Toddlers Suspected of Having Autism&quot;</i><br />Two-Year Award: $97,080<br />Research Partner: Toys R Us, Inc.</p><blockquote><p>Advances in psychological research of the core social deficits in autism have increasingly focused attention on disruptions of early-emerging skills that appear to derail from the normal development of socialization. However, there is a lack of quantifiable indices of social competence that could define a spectrum of social outcomes, from normality to varying manifestations of autism. This hinders genetic and neurofunctional research, which partially rely on such indices for interpretation of heritability and neuroimaging data.</p><p>This study, under the direction of Dr. Ami Klin, focuses on the inability of autistic children to visually orient themselves to social stimuli, and transfer that information to create mental representations. This process is a key requirement to subsequently produce normal social interactions. The investigators will use a novel method that measures visual scanning patterns in response to real life social interactions. A non-invasive eye-tracking device will measure the specific location in which an infant is focusing during social situations. The capacity of the infant to create mental representations can be evaluated via computerized animations. This strategy will also quantify any atypical strategies of social monitoring and will bring experimental measures into line with clinical observations.</p></blockquote><p><b>
<b>Jeffrey D. Macklis, M.D., D.<br />HST Children's Hospital/Harvard Medical School, Boston, MA</b>
</b><br /><i>&quot;Neocortical Callosal Projection Neuron Survival and Differentiation Control&quot;.</i><br />One-Year Award: $50,000<br />Research Partner: Audrey Flack &amp; H. Robert Marcus, on behalf of the Autism Society of America Foundation</p><blockquote><p>The major communication pathway between the two hemispheres of the brain is through the corpus callosum, where specific connections by cells called &quot;callosal projection neurons&quot; (CPN) are thought to underlie high-level associative cognitive function that is compromised in autism. There are both strong theoretical reasons and significant recent evidence to support the hypothesis that abnormal development of CPN could play an important role in autism spectrum disorders. Abnormalities of these neurons have been reported in autistic patients by multiple investigators. However, such analysis has been hampered by the overwhelming diversity of cell types and inability to isolate them.</p><p>In this study, Dr Jeffery D. Macklis and his colleagues have used a novel method, using retrograde fluorescence labeling and fluorescence-activated cell sorting (FACS), to successfully isolate CPN from mice. By isolating the purified CPN from embryonic and postnatal mice at distinct stages of development, they have shown that the purified CPN survive for weeks, acquire stage-specific morphologies, and express appropriate neurotransmitters and growth factor receptors. Furthermore, their studies have demonstrated that depending on the development stage at which the CPN are isolated, there is a dependence to exogenous factors. The researchers intend to build on this pilot data and elucidate which specific genes, both known and novel are differentially expressed during these progressive steps of development.</p></blockquote><p><b>
<b>Ron C. Michaelis, Ph.D. J.C.<br />Self Research Institute, Greenwood Genetic Center, Greenwood, S.C.</b>
</b><br /><i>&quot;Mapping the Breakpoints of a Balanced Translocation, t(9:15)(q32;q22), in a Patient with Autism&quot;.</i><br />Two-Year Award: $57,475<br />Research Partner: Pittsburgh Friends of NAAR</p><blockquote><p>Genetic studies indicate that many different genes are likely to contribute to the risk of developing autism and that the extent each of these genes are involved may vary from person to person. So, trying to determine which genes are related to autism is very complex. However, as noted bellow, there are some resent findings that may help in this effort.</p><p>Dr. Ron C. Michaelis has been working with an autistic individual who has a balanced genetic translocation involving chromosome 9 and chromosome 15; that is, pieces of DNA have broken off during early embryonic development and switched places. Individuals with balanced genetic translocations represent valuable resources for determining specific genes responsible for developmental disorders as these translocations usually result in disruption of the activity of a gene at the site of the translocation. To add to this, other studies have suggested that this region in chromosome 15 contains several genes that are potentially involved in autism. To identify the genes disrupted by the translocation, Dr. Michaelis and his collegues will physically map the translocation breakpoints and analyze the DNA sequence surrounding the breakpoints.</p></blockquote><p><b>
<b>Yan Ni, Ph.D.<br />University of Texas-Southwest Medical Center, Dallas, TX</b>
</b><br />NAAR/Bristol-Myers Squibb Research Fellowship in Autism and Neuropharmacology.<br />One-Year Award: $60,000</p><blockquote><p>Sertraline and fluoxetine are among the most effective drugs for alleviating irritability, aggression and repetitive behavior in autistic adults. These drugs affect the uptake of Serotonin (SHT). Presently, one of the best-replicated neurochemical changes in psychiatric research is the elevated blood SHT levels (hyperserotonemia) in autistic individuals. Since most (99%) of blood SHT is stored in the platelets (blood cells), hyperserotonemia studies have focused on SHT metabolism and platelet SHT uptake. The majority of evidence indicates that SHT metabolism is unaltered in autistic individuals. This strongly suggests that platelet handling of SHT is changed. However, despite much effort, no conclusions can currently be made regarding the rate of platelet SHT uptake in autistic patients.</p><p>Dr. Yan Ni hypothesizes that altered levels of platelet SHT in hyperserotonemic autistic patients are due to changes in function and/or expressions of the platelet 5HT uptake system and that altered expression levels of SHT transporters and SHT receptors will be present in the postmortem brain tissues from autistic patients. He and his collegues will assess the role of both pre- and post-synaptic components of the serotonergic system in autism. Specifically, they will examine whether there are changes in the function and expression levels of the SHT transporter.</p></blockquote><p><b>
<b>Jorge J. Prieto, M.D., Ph.D.<br />Universidad Miguel Hernandez (Spain)</b>
</b><br /><i>&quot;A Microscopical Study on the Neuroanatomical Abnormalities of Language-Related Cortical Areas in Autistic Patients&quot;.</i><br />Two-Year Award: $66,000<br />Research Partner: Nancy Lurie Marks Family Foundation</p><blockquote><p>Previous studies have demonstrated abnormalities in different parts of the brain in autistic individuals, including the cerebral cortex. Dr. Jorge Prieto hypothesizes that alterations in hearing and language may be due to a disorganization of cortical architecture. Working with tissue from the Autism Tissue Program, his research group will investigate the anatomy of neurological tissue of autistic brains. Several parameters will be investigated including the gross anatomical alterations of the auditory cortex, the microscopical organization of the cerebral cortex in the Wernicke and Broca's areas, and the possible changes in the cortical circuitry involving the pyramidal cells and interneurons. Through the techniques of stereology and immunocytochemistry, Dr. Prieto will attempt to elucidate the existence of morphological changes that could be responsible for the functional alterations and behavioral impairments seen in autism.</p></blockquote><p><b>
<b>Raju K. Pullarkat, Ph.D.<br />New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY</b>
</b><br /><i>&quot;Neurochemical Studies on Infantile Autism&quot;.</i><br />Two-Year Award: $49,973</p><blockquote><p>With the recent availability of frozen autopsy brain samples, it is now possible to carry out a systematic search for the neurochemical changes in autism. Dr. Raju K. Pullarkat has previously shown a consistent protein change in the brains of autistic individuals of different ancestory, one Asian-American, one African-American, and one Caucasian. In specific, they have found a 29 kDa protein is missing and another 36 kDa protein is present.</p><p>In this study, under the supervision of Dr. Raju K. Pullarkat's, the 29 kDa and 36 kDa proteins will be isolated and characterized and it will be determined whether abnormalities of these proteins can be used as diagnostic markers for autism. To reach this goal, these proteins will be purified using classical chromatographic approaches. In order to evaluate the diagnostic potential, levels of these proteins will be determined in cultured lymphoid cells from patients with autism, their parents, and their siblings. This study could also lead to the identification of a gene related to autism and aid in the development of a biochemical method of diagnosis.</p></blockquote><p><b>
<b>Moyra Smith, M.D., Ph.D.<br />University of California-Irvine, Irvine, CA</b>
</b><br /><i>&quot;Analysis of Chromosome 15q22 Deletion Associated with Autism and Immune Deficiency&quot;.</i><br />One-Year Award: $30,000 (continuation grant)</p><blockquote><p>In a prior research study funded by NAAR, under the direction of Dr. Moyra Smith (see 2001 sponsored research), it was suggested that the autistic behavior of the subject in the study was due to interruption or rearrangement of a specific series of genes within the 15q22-15q23-genome region. The present study focuses on the identification of the specific genes which when deleted or structurally rearranged can lead to altered neural development characteristic of autism. Through gene mapping and sequencing, this analysis will determine the relevance of the genes in the 15q22-q23 and the 15q11-q12 chromosomal regions to autism.</p></blockquote><p><b>
<b>James S. Sutcliffe, Ph.D.<br />Vanderbilt University Medical Center, Nashville, TN</b>
</b><br /><i>&quot;Modeling Autism-Related Chromosome 15 Duplications in the Mouse&quot;.</i><br />Two-Year Award: $100,000</p><blockquote><p>Genetic studies indicate that many different genes are likely to contribute to the risk of developing autism and that the extent each of these genes are involved may vary from person to person. So, trying to determine which genes are related to autism is very complex. However, there are some resent findings that may help in this effort. One such example is the finding that there is a small population within the autism community that have an extra copy of a portion of DNA on a chromosome. This results in a duplication of the genes in this area.</p><p>Dr James Sulcliffe and his collogues intend to use an approach, similar to one that has been proven to be successful in studying Down's Syndrome, to identify which genes within the duplicated segment of chromosome 15 are related to autism. They will generate several lines of mice that carry an extra copy of mouse or human DNA containing only one of the genes from the segment. Each of the lines will then be observed for behavioral and neurological changes. Each change that is related to autism can then be associated to the specific gene.</p></blockquote><p><b>
<b>Fred R. Volkmar, M.D. &amp; Katarzyna Chawarska, Ph.D.<br />Yale University Child Study Center, New Haven, CT</b>
</b><br /><i>&quot;Precursors of Joint Attention Skills in Autism and Related Conditions&quot;.</i><br />Two-Year Award: $62,337<br />Research Partner: Nancy Lurie Marks Family Foundation</p><blockquote><p>Most screening tools used for early identification of autism, include testing the capacity for sharing attention to an object of mutual interest. This is referred to as &quot;joint attention&quot; and is considered a key basic skill providing the foundation for communicative and social-cognitive development. Deficits in joint attention are profound and virtually universal in children with autism. Deficits are detectable in the second year of life, appear stable over time, and are independent from level of intelligence. However, the mechanisms underlying joint attention deficits are still poorly understood.</p><p>Dr. Fred Volkmar proposes to classify and measure the precursors of joint attention skills. In this study, he and his collegues will identify any differences in the profiles of infants with autism, developmentally delayed non-autistic children, and neurotypical children. In specific, they will investigate; a) the capacity to spontaneously follow the gaze of others to objects and events, b) the capacity for engaging in eye to eye attention with others, and c) using the gaze of others to regulate one&#213;s own behavior. This will elucidate the origins of gaze abnormalities in autism, and contribute to the design of new investigative instruments to discover autism in its early stages.</p></blockquote><p><b>
<b>Ching H. Wang, M.D., Ph.D.<br />University of Missouri, Columbia, MO</b>
</b><br />Roland D. Ciaranello, M.D.<br />Memorial Career Development Award in Basic Research.<br />Two-Year Award: $100,000</p><blockquote><p>To regulate the level at which any gene is expressed, many control factors have to be acting together to achieve the appropriate levels of power and refinement. Genes whose expression depends on parental origin are called &quot;imprinted genes&quot; and are controlled by DNA methylation, i.e. the addition of a small &quot;tag&quot; called a methyl group on one of the bases that make up the DNA code. Since two of the autism candidate loci, 7q31-32 and 15q11-13 both contain imprinted genes, it has been hypothesized that autism may ensue from the abnormal DNA methylation and expression of these genes.</p><p>Dr. Ching and his collegues intend to implement a novel approach to identifying methylated genes, termed &quot;differential methylation hybridization&quot;. Abnormally methylated areas will be isolated from DNA samples from autistic individuals, and compared (by hybridization) to control samples. Microarray membranes will then be used, and clones exhibiting abnormal hybridization will be identified and sequenced. These sequences will be used to search for associated genes in the genome database. Gene expression will be analyzed using autistic and control tissues, to confirm the abnormal function of these genes. This innovative approach will elucidate genetic information about autism unattainable through previous traditional techniques.</p></blockquote><p><b>
<b>Larry J. Young, Ph.D.<br />Emory University, Atlanta, GA</b>
</b><br /><i>&quot;An Oxytocin Knockout Mouse Model for Social Deficits&quot;.</i><br />Two-Year Award: $71,250</p><blockquote><p>The hormone oxytocin has been linked to cognitive and behavioral processes related to social attachment. Research suggests that maternal bonding, and pair bonding in monogamous species is attributed to oxytocin levels. Previous studies have found that autistic children have 50% less oxytocin than neurotypical children. Dr. Larry Young and his collegues intend to determine the relevance of oxytocin levels in autistic individuals. His group has previously shown that by decreasing oxytocin levels in mice resulted in isolation from mother and littermates along with a decreased recognition of littermates. Through the use of genetically engineered mice without the oxytocin gene, this project will determine the nature of the oxytocin deficit, and examine other social behaviors.</p></blockquote><p><b>
<b>Deborah A. Yurgelun-Todd, Ph.D.<br />McLean Hospital/Harvard Medical School, Boston, MA</b>
</b><br /><i>&quot;Visual Spatial Attention in Autism: An fMRI Study&quot;.</i><br />Two-Year Award: $82,259</p><blockquote><p>Autistic individuals show a marked deficit in the ability to rapidly shift visual attention between spatial locations and in engaging visual attention in the presence of distracters. The relations between regions of the brain that involved in directed attention have yet to be explored. In this study, Dr. Yurgelun-Todd and her colleagues will use functional magnetic resonance imaging (fMRI) to determine which parts of the brain are activated when autistic and non-autistic subjects view moving objects. Preliminary data presented at the 2001 International Meeting for Autism Research (IMFAR) show activation in non-autistic subjects include contralateral (opposite side) activity of the &quot;inferior occipitotemporal&quot; brain region, as well as ipsilateral (same side) activity of the posterior intraparietal &quot; brain region. Autisic individuals, however, show an absence of lateralised attentional activity in the occipitotemporal region and a higher level of lateralised attentional activity of the posterior intraparietal region. Dr. Yurgelun-Todd suggests that during conditions that demand a rapid shift of visual attention, autistic individuals compensate for their impaired selective attention with a generalized arousal that results in the input of more irrelevant stimuli.</p></blockquote>
ScienceAmi KlinAnn GernsbacherAtlantaBostonBoston University Medical SchoolCACTCynthia R. JohnsonD.DallasDavid G. AmaralDavisDeborah A. FeinEmory UniversityGAGene J. BlattGreenwoodGreenwood Genetic CenterHST Children's Hospital/Harvard Medical SchoolIra L. CohenJeffrey D. MacklisJohn N. ConstantinoMAMadisonMONew HavenNew York State Institute for Basic Research in Developmental DisabilitiesNJ)NYPAPh.D.Ph.D. & H. Hill GoldsmithPh.D. J.C.PittsburghRon C. MichaelisS.C.Scott E. HembySelf Research InstituteSt. LouisStaten IslandStorrsTXUMDNJ–Robert Wood Johnson Medical School (New BrunswickUniversity of California-DavisUniversity of ConnecticutUniversity of PittsburghUniversity of Texas-Southwest Medical CenterUniversity of WisconsinWashington University School of MedicineWilliam G. JohnsonYale University Child Study CenterYan NiGrantsGrantsFri, 06 May 2011 01:33:14 +0000pwhalen@gmail.com450 at https://www.autismspeaks.org2000 Grants Funded (CAN) https://www.autismspeaks.org/science/grants-program/research-we-have-funded/2000-grants-funded-can
Conditional neurotrophin knock-out mice as a model for the developmental neuropathology of autism
<p><strong>Schahram Akbarian, Ph.D., Massachusetts General Hospital (Young Investigator)</strong><br />Dr. Akbarian's group has recently generated a mutant mouse that lacks the developing brain neurotrophin-3 (NT-3), a growth factor molecule. The mice are viable and have a normal life span. However, their brains have some developmental abnormalities that, interestingly enough, have also been found in some cases of autism. These include abnormal shape and size of the cerebellum (a brain structure in the back of the brain involved in motor control and thought processing) and abnormalities in the prefrontal and cingulate cortex (a brain area that is important for emotion, social interaction and thought processing). It is possible that a mouse that lacks NT-3 in the developing brain may become one of the first animal models for autism. This project's goal is to clarify this hypothesis. An animal model of autism will be of great advantage for autism research, because it would allow for the testing of novel drugs as a potential treatment for autism.</p>
Sensory-motor and social-communicative symptoms of autism in infancy
<p><strong>Grace T. Baranek, Ph.D., University of North Carolina, Chapel Hill (Pilot Research)<br /></strong>Defining the diagnostic symptoms of autism in infancy and understanding the early course of development for infants with autism are essential components of the effort to find effective treatments and possible cures for this neurodevelopment disorder. The conventional diagnostic criteria that are appropriate for somewhat older children with autism cannot be applied to the screening or diagnosis of infants for autism due to their reliance on judgments about behaviors that do not typically emerge until developmental ages beyond infancy. Some early social-communicative behaviors such as pointing at objects to show them to others have proven useful in screening for autism at 18-24 months of age, based on work by Simon Baron-Cohen and his colleagues in England. In addition, recent work by the principal investigator of this project suggests that the sensory-motor behaviors of infants with autism differ from both infants developing typically as with an infants with other developmental disabilities as early as 9-12 months of age. For example, infants with autism mouthed objects excessively, responded less to novelty in the environment, showed more aversion to touch, and were less responsive to people calling their names as compared with other infants.</p>
Three-dimensional morphometry of the hippocampus in children with autism
<p><strong>Stephen R. Dager, M.D., University of Washington (Pilot Research)</strong><br />The co-investigators on this project have extensive experience applying 3-D morphometric methods to the adult brain and have undertaken pilot work developing electronic templates of 3-year-old healthy controls. This project will be undertaken as a new research focus for their group, which has no previous experience investigating autism. Dr. Geraldine Dawson is nationally recognized as an expert on autism and will provide expertise on neurodevelopmental aspects of autism to ensure this technique-driven project retains a clinical ground. A &quot;Neuroimaging of Autism&quot; grant funded through NICHD, has been the entree into the field of autism research for the neuroimaging group at the University of Washington. To date, they have performed MRI/spectroscopy studies on 28 3-year-old children with autism. This grant proposal will allow the investigators to apply high dimensional imaging analysis tools that they have developed to systematically map out the 3-D morphometry of children's hippocampal region. This process will generate data comparing autistic children with age-related controls at ages 3 to 4 years and again at ages 6 to 7 years when restudied.</p>
A non-human primate model to study prefrontal cortex dysfunction in autism
<p><strong>Stefan Everling, Ph.D., University of Western Ontario, Canada (Pilot Research)<br /></strong>A major problem in the search for the neural basis of autism is that many of the core symptoms like social isolation and language deficits are difficult or even impossible to investigate in animal models. Only recently, it has been discovered that autistic subjects have problems in a simple eye movement task. It was found that autistic subjects had no problems looking toward a spot of light, but it was very difficult for them to look away from the light. We believe that this finding can provide a new approach toward the investigation of the neural basis of autism, because eye movements can be investigated in monkeys. Monkeys and humans share all the brain areas that control eye movements and we already have a good understanding of the principal neural mechanisms that are necessary to move the eyes. This project will train monkeys on exactly the same eye movement task in which they see a spot of light and have to look the opposite way. The investigators will first identify the processes in the brain that occur when monkeys perform this task by recording the activity of single neurons in the brain. Then, the same behavior abnormality will be created in the animals that is found in the autistic subjects by deactivating and modulating the neural activity with substances that block the receptors of certain neurotransmitters that have been implicated in autism. This should provide insights into the brain mechanism that is altered in autism.</p>
Identification of autism-linked genomic regions by a genome-wide mapping and genetic study of chromosomal abnormality of 15q
<p><strong>Jianjun Liu, Ph.D., Columbia University (Young Investigator)</strong><br />Autism is a neuropsychiatric disease that occurs in 1 to 2 in 1000 children. Even though the physiological mechanism of autism is still not clear, scientific studies have shown that the development of autism is influenced by inheritable genetic factors. One of these genetic factors might locate in chromosome 15 because many cases have been reported indicating a possible association between the chromosomal abnormality of chromosome 15 and autism or autistic behavior. This project is proposed to further investigate this possible association in AGRE's families and, if the association is confirmed, to try to identify gene or genes that may increase the risk that a child will develop autism.</p>
A review paper on secular trends in the occurrence of autism
<p><strong>Craig Newschaffer, Ph.D., Johns Hopkins School of Public Health (Contracted Research)</strong><br />The goal of this project is to produce a research-review-style paper on trends in autism incidence of a quality suitable for publication in an academic journal. The paper will discuss available data (focusing on the most recent available information), explain epidemiological issues in the interpretation of such information, draw analogies from data on secular trends in the risk of a select set of other diseases initiating in early childhood, critically explore the coherence of the autism incidence data with current theories of autism causality, and make suggestions for research activities that would help improve our ability to accurately measure and interpret secular trends.</p>
Identification of candidate genes for involvement in autism
<p><strong>Stephen W. Scherer, Ph.D., Hospital for Sick Children (Canada) (Pilot Research)</strong><br />There is now overwhelming evidence of the importance of genetic factors in the etiology of autism. In fact, evidence points towards autism as being one of the neuropsychiatric disorders most influenced by genetic factors. Recent molecular genetic studies have found a region on human chromosome 7 that likely contains a gene which when mutated causes autism. Using cloning techniques, this project aims to identify this gene and develop a new research program in the molecular genetics of autism. The gene identification will provide insight into the basic molecular defect, allow for proper diagnosis and thoughtful family planning, and perhaps even lead to a treatment for autism.</p>
Molecular mechanisms of Fragile X syndrome: Understanding the function of the drosophila homologue of the Fragile X gene, FMRI
<p><strong>Haruhiko Siomi, Ph.D., University of Tokushima (Japan) (Pilot Research)</strong><br />Autistic features have been described in individuals with well-characterized genetic disorders, most notably fragile X syndrome. This suggests that there may be common mechanisms leading to the two disorders. Fragile X patients fail to make the protein product of the fragile X gene, fMR1. Animal models often provide us with great clues as to the mechanisms leading to given human genetic disorders. To elucidate the function of fMR1, we use the fruit fly as a model system since a plethora of new and old methodology is available that can be applied to questions involving complex behaviors such as learning and memory in fruit flies. Once we elucidate the function of the fruit fly fMR1, we can effectively begin to address the question of how the lack of fMR1 expression leads to symptoms including autistic features in fragile X syndrome.</p>
Detection of autism and Asperger's syndrome in 4-10 month old infants
<p><strong>Philip Teitelbaum, Ph.D., University of Florida (Treatment Award)<br /></strong>This group is developing methods to facilitate the early diagnosis of autism and Asperger's syndrome, as early as four months of age. In 25 out of 25 infants so far, that turned out later to be autistic, the group has found characteristic disturbances in their movement that can be useful to diagnose them early. In Asperger's syndrome, the movements are less disintegrated than in more severe autism, but movement disturbances are present in every child studied by us so far. We want to produce a self-explanatory video that can be made available to parents, pediatricians, and professionals that will help them to recognize these movement disturbances so that they can refer the children for careful observation and therapy by professionals skilled in the treatment of autism and Asperger's syndrome. We are also investigating the lateral head-righting reflex as a simple rapid diagnostic screening technique useful for pediatricians to test for autism in babies as early as 8-10 months of age.</p>
ScienceCanadaChapel HillColumbia UniversityCraig NewschafferGrace T. BaranekHaruhiko SiomiHospital for Sick ChildrenJianjun LiuJohns Hopkins School of Public HealthMassachusetts General HospitalPh.D.Philip TeitelbaumSchahram AkbarianStefan EverlingStephen R. DagerStephen W. SchererUniversity of FloridaUniversity of North CarolinaUniversity of TokushimaUniversity of WashingtonUniversity of Western OntarioGrantsGrantsFri, 06 May 2011 01:21:29 +0000pwhalen@gmail.com447 at https://www.autismspeaks.org2001 Awards (NAAR) https://www.autismspeaks.org/science/grants-program/research-we-have-funded/2001-awards-naar
<p>In 2001, NAAR broke new ground in terms of the amount of money committed to autism research and the number of projects funding. It also marked the first time the organization funded projects in Israel and Ireland, and included In 2001, NAAR committed approximately $3.1 million to fund 28 pilot studies, fellowships and programs, including its largest investment to date in a single project: The Baby Sibs Study &#8211; a collaborative, multi-site research program taking place in Canada and the U.S. Also in 2001, NAAR played a key role in funding and establishing the first annual International Meeting for Autism Research (IMFAR), the first international, interdisciplinary conference focusing on autism research.</p><p>Loisa Bennetto, Ph.D.<br />University of Rochester, Rochester, NY<br /><i>&quot;The Influence of HOX Genes and Cranial Nerve Abnormalities on Impaired Facial and Vocal Expression in Autism.&quot;</i><br />One-Year Award: $47,358</p><p>Dana Boatman, Ph.D., &amp; Barry Gordon, M.D., Ph.D.<br />John Hopkins School of Medicine, Baltimore, MD<br /><i>&quot;Evaluation of Auditory Processing in Low Functioning Children with Autism.&quot;</i><br />Two-Year Award: $85,606<br />Research Partner: The Doug Flutie, Jr. Foundation for Autism, Inc.</p><p>Linda Brzustowicz, M.D. &amp; Christopher Barlett, B.S.<br />Rutgers University, New Brunswick, NJ<br /><i>&quot;Localization of Genes Negatively Influencing Language Acquisition.&quot;</i><br />Two-Year Award: $89,606<br />First Year Research Partner: The Sidgmore Family Foundation</p><p>Edwin Cook, M.D.<br />The University of Chicago, Chicago, IL<br /><i>&quot;Linkage Disequilibrium Fine Mapping of 15q11-q13 in Autism.&quot;</i><br />Two-Year Award: $99,605<br />First Year Research Partner: Solving the Mystery of Autism Foundation</p><p>Louise Gallagher, MB MRC Psych<br />Trinity College, Dublin, Ireland<br /><i>&quot;The Molecular Genetics of Autism: Linkage Disequilibrium Screen in the Irish Population.&quot;</i><br />Two-Year Award: $99,101<br />First Year Research Partner: Autism Coalition for Research &amp; Education</p><p>Jeremy Goldberg, M.D.<br />McMaster University, Hamilton, Ontario (Canada)<br /><i>&quot;Investigating Serotonin Receptor Function and Brain Structure as Potential Endophenotypes of Autism.&quot;</i><br />Two-Year Award: $89,368</p><p>Andrew Grayson, Ph.D, C. Psychol.<br />The Open University (United Kingdom)<br /><i>&quot;Facilitated Communication: A Systematic Observational Research Project Involving Fine-Grained Video Analysis and Eye Tracking.&quot;</i><br />Two-Year Award: $93, 532.<br />Research Partner: Nancy Lurie Marks Family Foundation</p><p>Karl Herrup, Ph.D. <br />Case Western Reserve University, Cleveland, OH<br /><i>&quot;CNS Pattern Formulation and the Etiology of Autism.&quot;</i><br />Two-Year Award: $99,000</p><p>Christine Hohmann, Ph.D. <br />Morgan State University, Baltimore, MD<br /><i>&quot;Serotonin as Regulator of Cortical Development and Function.&quot;</i><br />Two-Year Award: $90,702<br />First Year Research Partner: Autism Coalition for Research &amp; Education</p><p>Huang Chi-ming, Ph.D.,<br />University of Missouri-Kansas City, Kansas City, MO<br /><i>&quot;Synaptic and Cellular Abnormalities in the Maturing Autistic Cerebellum.&quot;</i><br />Two-Year Award: $99,880<br />First Year Research Partner: Autism Society of America Foundation</p><p>Jeffrey Hutsler, Ph.D.,<br />University of Michigan, Ann Arbor, MI<br /><i>&quot;Cortical Organization and Synaptic Culling in Individuals with Autism.&quot;</i><br />Two-Year Award: $99,902</p><p>Ami Klin, Ph.D., &amp; Jocelyne Bachevalier, Ph.D., <br />Yale University Child Study Center, New Haven, CT<br /><i>&quot;Studies of Social Visual Pursuit in Non-Human Primates with Mesiofrontal-limbic Lesions Previously Shown to Offer a Successful Animal Model of Autism.&quot;</i><br />Two-Year Award: $91,730</p><p>Jennifer Levitt, M.D.<br />University of California-Los Angeles (UCLA) Neuropsychiatric Institute, Los Angeles, CA<br /><i>&quot;Cortical Complexity and 1H MRS Studies of Communication in Autism.&quot;</i><br />Two-Year Award: $97,044</p><p>Elena Maestrini, Ph.D.<br />University of Bologna, Bologna (Italy)<br /><i>&quot;Search for an Autism Susceptibility Gene on Chromosome 2q.&quot;</i><br />Two-Year Award: $80,340<br />First Year Research Partner: Autism Society of America Foundation</p><p>Henry Markram, Ph.D.<br />Weizmann Institute of Science, Rehovot, Israel<br /><i>&quot;Altered Inhibitory Microcircuits in Autism.&quot;</i><br />Two-Year Award: $96,800<br />Research Partner: Nancy Lurie Marks Family Foundation</p><p>Daniel McIntosh, Ph.D.<br />University of Denver, Denver, CO<br /><i>&quot;Core Affective Processes in Autism.&quot;</i><br />Two-Year Award: $99,237</p><p>Lisa Monteggia, Ph.D.<br />Utah Southwestern Medical Center, St. George, UT<br /><i>&quot;Analysis of the Role of the Methyl-CG Binding Protein in the Pervasive Development Disorder, Rett's Syndrome, Using Genetically Modified Mice.&quot;</i><br />Two-Year Award: $100,000</p><p>Stewart Mostofsky, M.D.<br />Kennedy Krieger Institute, Baltimore, MD<br /><i>&quot;Examination of a Deficit in Procedural Learning in Autism.&quot;</i><br />Two-Year Award: $88,968<br />First Year Research Partner: Autism Coalition for Research &amp; Education</p><p>Rhea Paul, Ph.D.<br />Southern Connecticut State University &amp; Yale University Child Study Center, New Haven, CT<br /><i>&quot;The Development of Prosody in Young Children with Autism and Related Conditions.&quot;</i><br />Two-Year Award: $97,024</p><p>Margaret A. Pericak-Vance, Ph.D.<br />Duke University Center for Human Genetics, Durham, NC<br /><i>&quot;Web-based Genetic Educational Efforts for Autism and Related Disorders.&quot;</i><br />One-Year Award: $41,912</p><p>Judith Innes Piggot, MRCGP, MRCP <br />Stanford University School of Medicine, Stanford, CA<br />Roland D. Ciaranello, M.D. <br />Memorial Fellowship in Basic Research<br />Two-Year Award: $100,000</p><p>Samuel Pleasure, M.D., Ph.D.<br />University of California-San Francisco, San Francisco, CA<br /><i>&quot;The Role of WNTS in Hippocampal Ventricular Zone Development.&quot;</i><br />Two-Year Award: $92,384</p><p>Timothy P.L. Roberts, Ph.D.<br />University of California-San Francisco, San Francisco, CA<br /><i>&quot;Neural Correlates of Phonological Processing in Autism: An MEG Investigation.&quot;</i><br />Two-Year Award: $96,273<br />First Year Research Partner: Nancy Lurie Marks Family Foundation</p><p>Neil Smalheiser, M.D., Ph.D.<br />University of Illinois, Chicago, Chicago, IL<br /><i>&quot;Circulating Reelin in Autism Spectrum Disorders.&quot;</i><br />Two-Year Award: $89,320</p><p>Kathleen Sulik, Ph.D.<br />University of North Carolina-Chapel Hill, Chapel Hill, NC<br /><i>&quot;CNS Dysmorphogenesis in a Mouse Knockout Model for an Autism Syndrome.&quot;</i><br />Two-Year Award: $100,000</p><p>Paul Thorsen, M.D., Ph.D.<br />Danish Epidemiology Sciences Centre at Aarhus University and Odense University Hospital, Denmark<br /><i>&quot;Risk Factors for Neurodevelopmental Disorders: MMR Vaccine &amp; Childhood Autism.&quot;</i><br />One-Year Award: $25,000<br />Research Partner: CIBC World Markets</p><p>Steven Zalcman, Ph.D.<br />UMDNJ - New Jersey Medical School, Newark, NJ<br /><i>&quot;Cytokines, Monoamines and Stereotypical Motor Activity.&quot;</i><br />Two-Year Award: $96,170</p><p>Lonnie Zwaigenbaum, M.D., Susan Bryson, Ph.D., Peter Szatmari, M.D., Wendy Roberts, M.D. <br />McMaster University, Hamilton, Ontario (Canada)<br /><i>&quot;Identifying Early Markers of Autism: A Longitudinal Study of Infant Siblings&quot;</i><br />Two-Year Award: $99,993<br />First Year Research Partner: Autism Society of America Foundation</p><p></td /><td width="95"></td> </td /> </tr /><tr></tr><td width="155" align="left" valign="top"></td> </td /> <td width="55"></td> </td /> <td width="505" align="left" valign="middle"></td> </td /> <td width="95"></td> </td /> </tr /><tr></tr><td width="155" align="left" valign="top"></td> </td /> <td width="55"></td> </td /></p>
ScienceAmi KlinAndrew GraysonC. Psychol.Christine HohmannDana BoatmanDaniel McIntoshEdwin CookElena MaestriniHenry MarkramHuang Chi-mingJeffrey HutslerJennifer LevittJeremy GoldbergJudith Innes PiggotKarl HerrupKathleen SulikLinda BrzustowiczLisa MonteggiaLoisa BennettoLonnie ZwaigenbaumLouise GallagherMargaret A. Pericak-VanceMB MRC PsychMRCGPMRCPNeil SmalheiserPaul ThorsenPeter SzatmariPh.DPh.D.Rhea PaulSamuel PleasureSteven ZalcmanStewart MostofskySusan BrysonTimothy P.L. RobertsWendy RobertsGrantsGrantsFri, 06 May 2011 01:13:14 +0000pwhalen@gmail.com446 at https://www.autismspeaks.org2001 Grants Funded (CAN) https://www.autismspeaks.org/science/grants-program/research-we-have-funded/2001-grants-funded-can
Early detection of autism
<p><strong>Jan Buitelaar, M.D., Ph.D., University Medical Center Utrecht (Pilot Research)<br /></strong>For both clinical and research reasons it is important to detect children with typical autism and with the broader phenotype of autism spectrum disorders at an age as early as possible. We have started to screen children of 14 months in the general population for possible autism, to identify these children, to perform a regular and systematic follow-up, and to establish a final diagnosis at the age of 3.5 year. Specific aims are to develop a reliable screening instrument to detect children at high-risk for autism at 14 months of age, to develop diagnostic criteria for autism under age 3 year, and to study the biologic, behavioral, cognitive and environmental correlates and predictors of development in children at high-risk for autism.</p>
To provide statistical support to manage autism files and conduct analyses on the AGRE database.
<p><strong>Rita Cantor, Ph.D., University of California, Los Angeles (Bridge Grant)</strong><br />A statistical technician will take the AGRE family structure, phenotype and genotype data files and merge them appropriately into genetic analysis files which have very fixed formats, and make these files available to interested investigators using a request process; generate information in response to requests; conduct analyses on the AGRE database suggested by individuals with no analytic infrastructure; and conduct analyses on the AGRE database suggested by UCLA investigators.</p>
To analyze the fluidity, cholesterol and phospholipid levels of platelets and erythrocyte ghost membranes in autism
<p><strong>Ved Chauhan, Ph.D., Institute for Basic Research in Developmental Disabilities (Bridge Grant)</strong><br />Several reports suggest that autism is a common neurological disorder among children. However, continuous scientific neglect of this disease has resulted in very few biochemical studies. The diagnosis of the disorder is done behaviorally. A biochemical marker for this disease is urgently needed to assist the behavioral diagnosis. We analyzed erythrocyte membrane fluidity in the blood samples from 7 autistic children, their siblings and parents. Interestingly, 86% of the autistic children showed a decrease in membrane fluidity as compared to their normal siblings and parents. Fluidity of the membrane is an index of microenvironment of the membrane that controls its biological functions. Normally, membrane fluidity decreases with age, and therefore, normal children are expected to have higher membrane fluidity as compared to their parents. Our preliminary results, therefore, suggest that autistic children follow an opposite pattern for membrane fluidity as compared to normal controls. We hypothesize that erythocyte ghost membrane fluidity is decreased in patients with autism, due to an imbalance in the phospholipid/cholesterol molar ratio, and that platelets may also be altered in autism.</p>
Language, autism and the brain: Insights from neuroimaging
<p><strong>Mirella Dapretto, Ph.D., University of California, Los Angeles (Pilot Research)</strong><br />Deficits in social communication are a hallmark feature of autism. Even in high-functioning autistic individuals, mastery of the formal aspects of language (e.g., phonology and syntax) is associated with deficits in understanding the communicative intentions of others, as conveyed in discourse and by the use of prosodic cues. Although several neuroimaging studies point to a number of structural and functional abnormalities in the autistic brain, thus far, no empirical study has focused on the brain circuitry involved in the persistent communicative deficits seen in autistic individuals, particularly in the pragmatic domain (i.e., the context-appropriate social use of language). Indeed, very little is known about the neural substrate of these high-level linguistic functions in the normal adult brain and even less about the functional and structural neural developments associated with the emergence of these communicative abilities in the normally developing brain. The proposed research will use functional and structural magnetic resonance imaging to (1) identify the networks of cortical activity associated with basic and complex linguistic functions in a sample of normally developing children; (2) examine how these neural networks change as a function of age and linguistic competence; (3) relate the developmental changes in the functional networks subserving language processing to age-related changes in brain morphometry; and (4) assess how the patterns of cortical activity, brain morphometry, and functional/structural relationships may be altered in a sample of high-functioning autistic children as compared to age- and gender-matched normal controls. <strong>First year funding partner: The Autism Coalition for Research and Education</strong></p>
Functional MRI of face processing in autism
<p><strong>Geraldine Dawson, Ph.D., University of Washington (Pilot Research)</strong><br />Research has demonstrated that individuals with autism have difficulty perceiving and remembering faces. Furthermore, one published study and our preliminary data indicate that the fusiform gyrus, a brain region involved in face perception, is not normally activated during viewing of unfamiliar faces in individuals with autism. These data suggest that abnormal functioning of the fusiform gyrus may be a biological marker of autism. However, it is unclear whether abnormal fusiform gyrus activation and its accompanying impairments in face recognition in autism represent a stable biological marker of autism, or are the secondary result of a lack of normal attention to and experience with faces. The proposed research will begin to address this question by determining whether activity of the fusiform gyrus in persons with autism can be readily modified through increased familiarity and expertise with visual stimuli. The goals of this project will be to: (1) Confirm our pilot fMRI data showing abnormal activation of the fusiform gyrus in individuals with autism; (2) Determine whether viewing of familiar faces (e.g., parents) yields greater fusiform activation than unfamiliar faces in individuals with autism; and (3) Determine whether training in the recognition of faces or objects leads to greater fusiform activation during the viewing of these trained stimuli. If greater familiarity or training leads to greater activation of the fusiform gyrus, this will be more consistent with an experience-driven neural abnormality hypothesis. Alternatively, if increased activation is not found, this will be stronger evidence of a stable biological marker in autism.</p><p><strong>Steward Flaschen Memorial Young Investigator Award:</strong></p>
The role of early environment in the regulation of oxytocin receptor expression and social behavior
<p><strong>Darlene Francis, Ph.D., Emory University (Young Investigator)</strong><br />The inability to form normal social attachments characterizes many forms of psychopathology, yet there has been little attention devoted to understanding the neural basis of social attachment and bond formation. We propose to investigate the neurobiology of social attachment and social bonding. The neuropeptide oxytocin has previously been implicated in the central mediation of attachment behaviors. It is important for the central control of social attachment behaviors as well as the expression of parental care. While cellular and molecular studies have begun to provide preliminary understanding of how oxytocinergic pathways are regulated, notably in the social prairie vole species, little attention has been devoted to the environmental regulation of this system. We will determine if within species differences in the oxytocin receptor system are related to differences in social behavior. We will then investigate the role the early postnatal environment (i.e. parental care) plays in the expression of this receptor system and the social behaviors associated with it. Conclusions: Autism, as with most other forms of psychopathology, is most likely the result of a fine interplay between our genes and our environments. The proposed experiments will allow us to begin to integrate the role of genes and gene regulation in the context of a known environment. Ultimately we wish to investigate the role of both the prenatal and postnatal environments and their relationship to genes implicated in the regulation of social attachment.</p>
The gut, serotonin, secretin and autism
<p><strong>Michael Gershon, M.D. Columbia University (Bridge Grant)</strong><br />Peripheral serotonin concentrations are often elevated in autistic children, and some children have benefited from treatment with exogenous secretin. This study will measure the number of secretin and serotonin-producing cells in intestinal biopsies of autistic children and normal controls, measure the content of SERT, and measure the expression of the duodenal 5-HT3 receptor. Through his rediscovery of the &quot;second brain&quot; nerve cells in the gut that act as a brain, Dr. Gershon has helped bring the emerging field of neurogastroenterology to the forefront of modern medicine.</p>
To develop a prototype communication accessor system with the Archimedes Project at Stanford's Center for the Study of Language and Information.
<p><strong>Dan Gillette, Ed.M., Stanford University (Contracted Research)</strong><br />For many affected by autism, verbal communication is extremely difficult. Though many children with autism learn to speak and read, their path is often not an easy one. Recently, there have been significant technological advances that make it possible to build truly useful and portable communication systems devices with off-the-shelf components. With the introduction of handheld computers and the rapid expansion of the Internet and World Wide Web, attention can now be focused on adapting technology to effectively aid verbal communication.</p>
A family study of hyperlexia in autism
<p><strong>Elena Grigorenko, Ph.D., Yale University (Pilot Research)</strong><br />Five-to-ten percent of autistic children manifest hyperlexia-an ability to read and decode single words beyond the expected level based on the level of the child's IQ. In the context of otherwise retarded cognitive functioning, this ability is rather striking and deserves thorough and detailed investigation. The potential interventional importance of hyperlexia is difficult to underestimate: the engagement of reading and fascination with a printed symbol demonstrated by children with hyperlexia suggest that printed symbols may be used as a vehicle for communicating instructions. Currently, however, very little is known about hyperlexia. The long-term objective of this project is a better understanding of the etiology of autism, in particular, autism with hyperlexia. The data we collect will make it possible to characterize more completely the nature of the relationship between autism and hyperlexia. We propose to collect a sample of 20 families of hyperlexic autistic probands, 20 families of autistic probands without hyperlexia (gender- and age-matched to the hyperlexia sample), and 20 control families of gender- and age- matched controls. Studying these families should help to clarify further the transmission of autism and enhance our understanding of the phenomenon of hyperlexia as well as the familial relationships between autism and hyperlexia. In all cases, information will be obtained by direct structured assessment of all pertinent family members. These assessments will include an extensive neuropsychological assessment, structured interviews for the assessment of autism and related conditions, and structured psychiatric interviews for the documentation of all major psychiatric disorders. <strong>First year funding partner: The Autism Coalition for Research and Education</strong></p>
To support research on the mechanisms and molecules important for prenatal development of the cerebral cortex.
<p><strong>Tarik Haydar, Ph.D., Yale University, (Bridge Grant)</strong><br />Dr. Haydar, a postdoctoral fellow in Dr. Pasko Rakic's laboratory, is working on the reasonable assumption that understanding the mechanisms of neurogenesis in humans is an essential step for designing the cure or treatment for disorders such as autism.</p>
Functional and diffusion tension imaging in autism
<p><strong>Nancy Isenberg, M.D., Ph.D., JFK Institute Medical Center (Pilot Research)</strong><br />Social cognitive deficits are a critical feature of autism. Based on animal lesion, single-cell recording, and neurological studies, a specialized neural circuit centered on the amygdala, and involving orbitofrontal cortex, anterior cingulate and superior temporal sulcus, has been proposed to underlie social cognition. In order to identify the neural systems which are disordered in the social cognitive deficits in autism, we will utilize event-related fMRI along with a probe, piloted in healthy subjects, that reliably activates an amygdala circuit, relevant for the evaluation of and response to interpersonal, linguistic threat. Linguistic threat processing is an aspect of social cognition with evolutionary significance and is therefore more likely than other cognitive tasks, such as theory of mind, to target phylogenetically older limbic structures, such as the amygdala, which have been implicated neuropathologically in autism. In addition, we will perform diffusion tensor MRI in patients with autism and matched controls to further characterize white matter abnormalities that may also result in disturbances in functional connectivity between limbic and prefrontal areas thought to be relevant for social cognition. Understanding which neural systems are involved in the social cognitive deficits in autism will allow for the development of more appropriate interventions and new treatments. Pilot data provided by this study will be used as the basis for submission of an NIH career development award.</p>
A comparative study evaluating the dose-responsiveness effects of methylmercury and thimerosal on select nervous, immune and enzyme parameters
<p><strong>Deborah Keil, Ph.D., Medical University of South Carolina (Environmental Factors of Autism)</strong><br />Infantile autism (IA) is a neurodevelopmental syndrome found in 1-5 cases of every 10,000 children with boys acquiring this syndrome 3-5 times more than girls. The spectrum of disorders of autism includes a range of impaired development of language and communication, unusual behaviors, and mental retardation. A diversity of pathophysiological effects also exist to include hyperserotoninemia, decreased T-cell proliferative function and activation, increased soluble IL-2 levels in serum, decreased CD8+ cells, decreased NK cells, development of anti-brain autoantibodies, decreased cerebellum volume and Purkinje cell number. Several studies indicate that the etiology of IA is multi-factorial and includes exposure to environmental chemicals. In particular, mercury exposure during infant and child development has been implicated in IA, especially in the case of vaccines containing mercury. Although mercury exposure from vaccines has been implicated in autism, this association has been criticized due to a lack of supportive experimental dose-response data. Thus, the proposed study will assess the possible role of methylmercury (MeHg) and thimerosal (TH) in contributing to the pathophysiology of IA using a mouse model to assess dose-responsive effects in cognitive and physiological parameters that encompass nervous, immune and enzyme pathways. This comparative approach will permit increased understanding of deficits due to MeHg or TH after acute exposure during early developmental stages and facilitate understanding of etiological causes of autism or other neurodevelopmental diseases. Furthermore, this study will also improve our understanding of the health effects attributed to different forms of mercury and contribute to the development of toxicological risk assessment models for detecting environmental contaminants that would adversely impact children's health.</p>
To support a five-year longitudinal study of 300 infant siblings of children with idiopathic autism.
<p><strong>Rebecca Landa, Ph.D., Kennedy Krieger Center for Autism and Related Disorders (Bridge Grant)</strong><br />Participants will be assessed at 6-, 14-, 24- and 36-month age levels. It is an important objective of this study to assess changes in the strength of association between predicators and outcomes, and hopefully document the possibility of autism diagnosis as early as 14 months of age. These findings will be critical to understanding the developmental course of autism spectrum disorders, early diagnosis, and guidelines for intervention. First year funding partner: The Autism Coalition for Research and Education</p>
To provide biomathematical support to do a comprehensive analysis of the current AGRE database.
<p><strong>Ken Lange, Ph.D., University of California, Los Angeles (Bridge Grant)</strong><br />A biomathematician will take the AGRE data and do more comprehensive check for pedigree relationship errors (this will involve comparing theoretical and empirical kinship coefficients for each pair of relatives in the data); do a gamete competition test for association of each marker with autism; do a bivariate QTL analysis of the two traits: time to first word and the obsessive-compulsive measure (this may strengthen the evidence for a QTL locus on chromosome 7); and do a nonparametric linkage analysis of the data using autism as a qualitative trait.</p>
Computer-assisted language training for children with autism
<a id="massaro"></a><p><strong>Dominic Massaro, Ph.D., University of California, Santa Cruz (Innovative Technology for Autism Award)</strong><br />The goal of the proposed research is to evaluate the potential for computer-assisted speech and language tutors to train and develop language skills with autistic children. Our language-training program utilizes a computer-animated talking head as the conversational agent, Baldi, who guide's students through a variety of exercises designed to develop lexical and phonological awareness. We propose to develop a motivational language tutorial program capable of introducing classroom curriculum and training and developing language and listening skills. Our research is a three-part process in which we will, 1) develop the necessary applications, 2) implement the applications in the curriculum of both the Bay School and Natural Bridges Elementary, and 3) evaluate the progress of the program.</p><p>Effective programs for this population share the following elements: (a) curriculum addressing the ability to use and comprehend language, and interact socially, (b) highly supportive teaching environments and generalization strategies, and (c) classroom environments that are predictable and routine. We believe full integration of the language tutors into the curriculum will greatly enhance the language development of children with autism. We believe this program holds promise for this population, our confidence derived from the success the program has witnessed not only at TMOS, but also with our preliminary work with these children.</p>
Sensorimotor gating in autistic disordered adults
<p><strong>William Perry, Ph.D., University of California, San Diego (Pilot Research)</strong><br />There is considerable evidence that Autistic Disorder (AD) results from abnormal brain development and yet the specific brain abnormalities that account for the social, behavioral, communication and cognitive deficits of AD remain unknown. There is evidence to suggest that some autistic symptoms can best be explained as a disorder of filtering or &quot;gating&quot; of sensorimotor information. Sensorimotor gating in AD can be studied using prepulse inhibition (PPI) of the human startle reflex, an operational measure of sensorimotor gating. This approach will be particularly informative because there are existing models for understanding the neural circuitry of startle gating, and startle gating deficits are associated with cognitive deficits in specific neurodevelopmental disorders.</p><p>The first objective of this proposal is to determine whether PPI deficits occur in AD adults. A second objective is to correlate PPI to behavioral, and neuropsychological measures. The final objective of this proposal is to develop the optimal PPI parameters for use in a functional neuroimaging (fMRI) setting so that the regional brain activity associated with deficient startle gating can be determined.</p><p>Twenty-five carefully diagnosed AD and 25 age and I.Q.-matched normal adults will be assessed using unimodal acoustic and tactile (air-puff) PPI paradigms. Neuropsychological tests of executive function, attention and vigilance will be administered. PPI will be assessed and correlated to behavioral (i.e., symptom) and neuropsychological performance. Based upon these results, a unimodal tactile PPI paradigm will be piloted for use in a fMRI setting.</p>
Diagnosis and treatment of attentional abnormalities in children with autism using an automated multimedia video game
<p><strong>Bertram Ploog, Ph.D., College of Staten Island/CUNY (Innovative Technology for Autism Award)</strong><br />Stimulus overselectivity is an attentional dysfunction, common in autistic individuals, which may seriously impair their social and academic functioning. We assume that behavior analysis can make significant contributions to the brain sciences and that early behavioral intervention may impact brain development and function. This proposal is aimed at improving our understanding of the attention processes involved in stimulus overselectivity and designing a treatment which employs audio-visual computer and Internet technology. The proposed study employs an experimental paradigm (a simple concurrent schedule of reinforcement) based upon behavior analytical principles, to explore factors which are involved in stimulus overselectivity. The paradigm is used to manipulate and test a variety of stimuli that differ in modality, quantity, quality, frequency, intensity, complexity, and discriminability. By incorporating the paradigm into a video game, the training and testing procedures will be enjoyable for the children, the procedures can be fully automated (reducing the need for professional involvement), and remediation procedures can be built into the game. Since the game is based upon &quot;off the shelf&quot; computer technology, and will be Internet accessible, it should provide affordable opportunities for remediation for a large group of affected children.</p>
A neurobehavioral and neurophysiological examination of motor function in autism and Asperger's disorder
<p><strong>Nicole Rinehart, Ph.D. Monash University (Victoria, Australia) (Young Investigator)</strong><br />Problems with motor functioning are a well known, but poorly understood, aspect of autism and Asperger's disorder. The aim of this research is thus to provide neurobehavioural and neurophysiological measures to quantify and qualify motor disturbance in these disorder groups. Recent retrospective studies have shown that even as infants, children with autism exhibit clear features of motor disturbance, which, if detected and clearly defined, could advance early diagnosis. In addition to advancing the clinical definition of autism and Asperger's disorder, a careful examination of motor disturbance may also illuminate the neurobiological underpinnings of these disorders. For example, recent evidence has shown that individuals with autism and Asperger's disorder have problems at the planning or initiation stages of motor functioning which may signify neural disruption within the basal-ganglia thalamocortical circuitry, for example, deficiencies in basal ganglia output to the supplementary motor area (Rinehart, Bradshaw, Brereton, &amp; Tonge, in press). This study will consist of three separate experimental paradigms. Experiment 1 will utilise a digitised tablet kinematics task to provide a comprehensive analysis of the following features of motor function in a group of young people with autism and Asperger's disorder: movement time, peak velocity, movement acceleration, and movement deceleration. Experiment 2 will use a Clinical Stride Analyser to examine cadence and stride length in young children with autism and Asperger's disorder. Finally, Experiment 3 will use a movement-related potentials (EEG) technique devised by Cunnington, Iansek, Johnson, and Bradshaw (1997) to measure brain activity during the preparatory and execution phases of movement in these disorder groups. <strong>First year funding partner: The Autism Coalition for Research and Education</strong></p>
Role of cytokines in developmental neurotoxicity
<p><strong>Ellen Silbergeld, Ph.D., University of Maryland School of Medicine (Environmental Factors of Autism)</strong><br />Methyl mercury (MeHg) is an environmental pollutant that causes profound neurotoxicity and has been associated with autism. A major toxic effect associated MeHg exposure in humans is damage to the developing nervous system, involving inhibition of cell migration. This project will test the hypothesis that methyl mercury disrupts neurodevelopment through perturbing cytokine-directed neural migration, resulting in permanent structural alterations of the CNS and behavioral and cognitive dysfunction. By defining the role of inflammatory cytokines in brain development, the results of this project may also have implications for understanding mechanisms by which maternal infections increase risks of autism and other perinatal brain disorders.</p>
Confirmation of the association and linkage of HLA genes in autism
<p><strong>Anthony Torres, M.D., Utah State University (Contracted Research)</strong><br />Numerous immune abnormalities have been noted in subjects with autism. The Reed Warren Memorial Laboratory at Utah State University has reported associations between autism and genes in the human leukoctye antigen (HLA) region on chromosome 6. Besides being the most gene rich region in the human genome, HLA genes encode many proteins with critical immune response functions. More diseases have associations with HLA genes than any other region in the human genome. Recently we have been able to link HLA-DR4 to autism by HLA-typing entire families. The transmission disequilibrium test (TDT) indicates that the probands inherit the HLA-DR4 allele more often from the fathers than would be expected. Linking HLA-DR4 to autism expands out knowledge between the immune system and autism. Our project with Cure Autism Now is very important, as research until this time has been with a limited number of probands and families mainly from Utah. Increasing the HLA database with several hundred additional families through Cure Autism Now and the Autism Genetic Resource Exchange (AGRE) will add significant power to our theory of autoimmune mechanisms in autism. First year funding partner: The Autism Coalition for Research and Education</p>
Social interaction abnormalities in dishevelled-1 mutant mice
<p><strong>Anthony Wynshaw-Boris, M.D., Ph.D., University of California, San Diego (Pilot Research)</strong><br />Numerous studies have demonstrated a strong familial tendency in autism, but no genes important for autism have been isolated. An alternative is to study animal models containing defined genetic mutations that display characteristics of autism. Studies of such mice may provide novel insights into processes that influence behavioral variation and aspects of human neuropsychiatric disorders. We have produced mice completely deficient for Dvl1 that surprisingly exhibit reduced social interaction and abnormalities of sensorimotor gating. The novel behavioral abnormalities displayed by Dvl1-deficient mice make them a potential genetic model for aspects of several human psychiatric disorders including autism. Therefore, we propose to examine the Dvl1-deficient mice in detail to try to identify abnormalities in neuronal morphology or function. To determine whether behavioral phenotypes are due to developmental abnormalities or adult signaling defects, we are producing conditional knock-out alleles to inactivate Dvl genes in a spatially and temporally restricted pattern during development, or in the adult. To understand the pathways that mediate the effects of Dvls on behavior, we will also use the Dvl1 homozygous mice as a sensitized strain to screen for genetic suppressors of the social interaction and sensorimotor gating phenotype. We will use cDNA microarray analysis to compare regional brain patterns of gene expression in wild-type and mutant mice throughout development. Patterns of global gene expression will be compared to try to identify regulatory pathways important for the Dvl1 mutant behavioral phenotype.</p>
Effect of mercury on apoptosis of neuronal cells
<p><strong>Leman Yel, M.D., University of California, Irvine (Environmental Factors of Autism)</strong><br />Organic mercury compounds are known to be toxic mainly to the nervous system. Recently, the similarities between the neurological findings in mercury exposure and autism have come to attention. It has been estimated that children are exposed to a quantity of mercury that exceeds the safety guidelines in the first two years of life through thimerosal (ethylmercury salicylate) in vaccines. And, a strong association between the administration of certain vaccinations and the onset of autistic manifestations has been noted. Autism is a multi-factorial disease in the pathogenesis of which genetic, immunological, and environmental factors play a role. Brain biopsies from autistic children show degeneration and a loss of neuronal cells without any evidence of inflammation that is consistent with an apoptotic (programmed cell death) process. Mercury accumulates in the mitochondria and disrupts cell energetics. It has been shown to induce apoptosis by causing mitochondrial dysfunction in lymphocytes. No study has been published on the apoptotic effect of mercury in the nervous system. We hypothesize that mercury induces apoptosis in neuronal cells and this effect is mainly via the mitochondrial pathway. This might be more pronounced in children with autism because of genetic susceptibility. Thus, apoptosis due to mercury exposure may contribute to the pathogenesis of autism. Therefore, we intend to examine the effect of thimerosal on apoptosis induction and the signaling steps of mitochondrial pathway of apoptosis in neuronal cells. The results would clarify the effect of a mercury compound in neuronal cell death and degeneration, and provide a better understanding of the potential role of mercury exposure in the pathogenesis of autism.</p>
A study of behaviors associated with fever in children with autism
<p><strong>Andrew Zimmerman, M.D., Kennedy Krieger Institute (Pilot Research)</strong><br />Salient behavioral characteristics of autism include underdeveloped communication skills, limited social interactions and repetitive activities. Clinician and parent reports suggest that fever may be associated with behavioral improvements in children with autism. The improvements may decline toward baseline when the fever subsides. The objective of this pilot study is to advance our understanding of the neurobiology of autism. The specific aims of this study are: 1) to assess if fever is associated with behavioral improvements in children with autism, and 2) to characterize the types and frequencies of these changes.</p><p>Study participants are children between the ages of six and eighteen years with a diagnosis of autism who are members of Autism Society of America chapters in the Baltimore-Washington area. Parents will take their children's temperatures each day with skin tapes and call research staff on the first day a child has a fever. Trained staff will visit the home that day and perform a behavioral test, the Autism Diagnostic Observation Schedule (ADOS). The ADOS will be performed with the child on two additional occasions: 1) one to two days later when the fever is declining, and 2) one week later when the child has not had a fever for a week. Comparison ADOS data will be collected on three days in a parallel time sequence for age- and sex-matched children with autism who do not get fevers over the study period. A second comparison group of non-autistic siblings of the &quot;febrile&quot; participants with autism will be studied as well.</p>
Research and design of accessibility tools for those with autism (2001-2003)
<p><strong>Archimedes Access Research and Technology International, Inc. (AARTI) (Contracted Research)</strong><br />Research the efficacy of computer accessors in regard to computer assisted communication for the autistic by creating and testing a communicator prototype. This study will include subjects fitting a range of competencies, including the more severely impacted.</p>
ScienceAndrew ZimmermanAnthony TorresAnthony Wynshaw-BorisBertram PloogDan GilletteDarlene FrancisDeborah KeilDominic MassaroEd.M.Elena GrigorenkoEllen SilbergeldGeraldine DawsonJan BuitelaarKen LangeLeman YelMichael GershonMirella DaprettoNancy IsenbergNicole RinehartPh.D.Rebecca LandaRita CantorTarik HaydarVed ChauhanWilliam PerryGrantsGrantsFri, 06 May 2011 00:53:13 +0000pwhalen@gmail.com445 at https://www.autismspeaks.org2002 Mentor-based Fellowships (NAAR) https://www.autismspeaks.org/science/grants-program/research-we-have-funded/2002-mentor-based-fellowships-naar
<p>In 2002, NAAR budgeted an unprecedented $1 million to fund pre- and post-doctoral mentor-based fellowships to attract the best and brightest young minds to focus their talents on autism research.</p><p><b>
<b>Pre-Doctoral Fellowships</b>
</b></p><p>Autism Research Centre (Cambridge, England)<br />Mentor: Simon Baron-Cohen, Ph.D.</p><p>University of Connecticut (Storrs, CT)<br />Mentor: Deborah A. Fein, Ph.D.</p><p>New England Medical Center (Boston, MA)<br />Mentor: Susan Folstein, M.D. <br />Research Partner: The Mellanby Autism Foundation</p><p>University of Illinois &#8211; Chicago (Chicago, IL)<br />Mentor: John A. Sweeney, Ph.D.</p><p>Yale University School of Medicine (New Haven, CT)<br />Mentors: Fred R. Volkmar, M.D. &amp; Rhea Paul, Ph.D.</p><p><b>
<b>Post-Doctoral Fellowships</b>
</b></p><p>University of Texas &#8211; Houston (Houston, TX)<br />Mentor: Jocelyne Bachevalier, Ph.D.</p><p /><p>Yale University School of Medicine (New Haven, CT)<br />Mentor: Pasko Rakic, M.D., Sc.D.</p><p>University of California &#8211; San Francisco (San Francisco, CA)<br />Mentor: John L.R. Rubenstein, M.D., Ph.D. <br />This fellowship is dedicated in memory of Dr. Roland D. Ciaranello</p><p>Yale University School of Medicine (New Haven, CT) <br />Mentor: Robert T. Schultz, Ph.D. <br />This fellowship is dedicated in honor of Dr. Marie Bristol-Power.</p><p>University of Illinois &#8211; Chicago (Chicago, IL) <br />Mentor: John A. Sweeney, Ph.D.</p><p>Boston University School of Medicine (Boston, MA)<br />Mentor: Helen Tager-Flusberg, Ph.D.</p><p>Yale University School of Medicine (New Haven, CT)<br />Mentor: Ami Klin, Ph.D.<br />Research Partner: CIBC World Markets</p><p></td /><td width="95"></td></td /></td /></tr /><tr></tr></tr /><td width="155" valign="top" align="left"></td></td /></td /><td width="55"></td></td /></td /><td width="505" valign="middle" align="left"></td></td /></td /><td width="95"></td></td /></td /></tr /><tr></tr></tr /><td width="155" valign="top" align="left"></td></td /></td /><td width="55"></td></td /></td /></p>
ScienceAmi KlinAutism Research CentreBoston University School of MedicineCIBC World MarketsDeborah A. FeinFred R. VolkmarHelen Tager-FlusbergJocelyne BachevalierJohn A. SweeneyJohn L.R. RubensteinM.D. & Rhea PaulNew England Medical CenterPasko RakicPh.D.Robert T. SchultzSc.D.Simon Baron-CohenSusan FolsteinThe Mellanby Autism FoundationUniversity of California – San FranciscoUniversity of ConnecticutUniversity of TexasYale University School of MedicineGrantsGrantsFri, 06 May 2011 00:35:21 +0000pwhalen@gmail.com444 at https://www.autismspeaks.org2002 Research Awards (NAAR)https://www.autismspeaks.org/science/grants-program/research-we-have-funded/2002-research-awards-naar
<p>In 2002, NAAR continued to drive the autism research movement and elevate the science more than any other autism organization, committing approximately $4 million to fund 22 pilot studies in autism research taking place in the U.S., England, Italy and Germany; three larger, collaborative programs in the U.S., Canada and England and 12 mentor-based fellowships in the U.S. and England. Also in 2002, NAAR played a key role in funding and presenting the first Canadian Autism Research Workshop, designed to enhance and increase autism research efforts in Canada.</p><p><b>
<b>2002 PILOT STUDY GRANTS</b>
</b></p><p>Schahram Akbarian, M.D., Ph.D. <br />University of Massachusetts Medical School, Worchester, MA<br /><i>Chromatin-Remodeling in Developing Prefrontal Cortex Implications for Autism</i><br />Two-year award - $120,000</p><p>Gillian Baird<br />St. Thomas Hospital HNS &amp; Guy's Hospital, London, England<br /><i>Is there Evidence of Antibodies Against Neural Tissue In Children with Autism?</i><br />Two-year award - $106,629<br />Research Partner: Solving the Mystery of Autism Foundation</p><p>Pradeep G. Bhide, Ph.D.<br />Harvard Medical School/Massachusetts General Hospital, Charlestown, MA<br /><i>Dopamine &amp; Brain Development: Implications for Autism Spectrum Disorders</i><br />Two-year award - $120,000<br />Research Partner: Richard &amp; Susan Smith Family Foundation</p><p>C. Susan Carter, Ph.D.<br />University of Illinois &#8211; Chicago, Chicago, IL<br /><i>Oxytocin &amp; Autism: An Animal Model</i><br />Two-year award - $120,000<br />Research Partner: Friends of Autism</p><p>Anna Dunaevsky, Ph.D. <br />Brown University, Providence, RI<br /><i>Synaptogenesis in Cerebellar Purkinje Cells of Normal &amp; FMR1 Knockout Mice</i><br />Two-year award - $120,000<br />Research Partner: FRAXA Research Foundation</p><p>Judith K. Grether, Ph.D.<br />California Department of Health Services &#8211; Environmental Health Investigations, Oakland, <i>CA Epidemiology of Autism in Multiple Births</i><br />Two-year award - $119,998<br />Research Partner: Autism Coalition for Research &amp; Education</p><p>Martha R. Herbert, M.D., Ph.D.<br />Massachusetts General Hospital, Boston, MA<br /><i>Neuroimaging of Young Children at High Risk for Autism</i><br />Two-year award - $119,280<br />Research Partner: Nancy Lurie Marks Family Foundation</p><p>Yong-hui Jiang, M.D.<br />Baylor College of Medicine, Houston, TX <br /><i>Epigenetics Alterations &amp; Autism Susceptibility</i><br />Two-year award - $119,350</p><p>Flavio Keller, M.D. Liberia<br />Universita, Rome, Italy<br />Reelin as a Target of Interaction between Genotype &amp; Environment in Autistic Disorder <br />Two-year award - $103,800</p><p>David E. Mandelbaum, M.D., Ph.D.<br />UMDNJ &#8211; Robert Wood Johnson Medical School, New Brunswick, NJ<br /><i>A Longitudinal Analysis of the Neurological Findings in Children with Autism, with High or Low IQ, and Comparisons to Non-Autistic Children with Developmental Language Disorder and Mental Retardation</i><br />One-year award - $34,210<br />Research Partner: Autism Coalition for Research &amp; Education</p><p>L. Alison McInnes, M.D.<br />Mt. Sinai School of Medicine, New York, NY<br /><i>A Population Genetic Study of Autism in Andalusia, Spain</i><br />One-year award - $57,993</p><p>Letitia R. Naigles, Ph.D. <br />University of Connecticut, Storrs, CT<br /><i>The Development of Language Comprehension in Children with Autism: A Longitudinal Study Using the Intermodal Preferential Looking Program</i><br />Two-year award: $119,987<br />Research Partner: Nancy Lurie Marks Family Foundation</p><p>Dennis D.M. O'Leary, Ph.D.<br />Salk Institute for Biological Studies, La Jolla, CA<br /><i>Molecular Control of Inferior Olive Development &#8211; A Step Towards Understanding the Neuropathology of Autism</i><br />Two-year award - $120,000<br />Research Partner: Autism Coalition for Research &amp; Education</p><p>Opal Ousley, Ph.D. &amp; Lisa A. Parr, Ph.D. <br />Emory University School of Medicine, Atlanta, GA<br /><i>Physiological Responsiveness to Social Interaction in Young Children with Autism</i><br />Two-year award - $90,725</p><p>David L. Pauls, Ph.D.<br />Harvard Medical School/Massachusetts General Hospital, Charlestown, MA<br /><i>A Genetic Study of High-Functioning Autism and Asperger Syndrome in Finland</i><br />Two-year award - $120,000<br />Research Partner: In Memory of Lisa Fenn Gordenstein</p><p>Nicholas Ponzio, Ph.D. <br />UMDNJ &#8211; New Jersey Medical School, Newark, NJ<br /><i>Contribution of Immunological Mechanisms to Autism Spectrum Disorders</i><br />Two-year award - $118,800<br />This project is dedicated in memory of Dr. Don C. Wiley</p><p>Hugo Theoret, Ph.D.<br />Harvard Medical School/Israel Deaconess Medical Center, Boston, MA<br /><i>Motor Output &amp; Mirror Cell Systems in Autism Studied by Transcranial Magnetic Stimulation</i><br />Two-year award - $116,401<br />Research Partner: Nancy Lurie Marks Family Foundation</p><p>Poul Thorsen, M.D., Ph.D.<br />Aarhus University, Denmark<br />Risk Factors for Neurodevelopmental Disorders: MMR Vaccine &amp; Childhood<br />Autism<br />Two-year award - $80,300</p><p>Chandan J. Vaidya, Ph.D.<br />Children's National Medical Center/Children's Research Institute, Washington, D.C.<br /><i>Using Functional MRI to Examine Social &amp; Non-social Attention Regulation in Autism</i><br />Two-year award - $97,792</p><p>Christoph Schmitz, M.D.<br />RWTH University at Aachen, Aachen, Germany<br /><i>Quantitative Analysis of Histologic Alterations in Cerebral Cortex, Cerebellum &amp; Brainstem in Autism</i><br />Two-year award: $98,700</p><p>Jerzy Wegiel, VMD, Ph.D.<br />New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY<br /><i>Clinicopathological Correlations in Autism</i><br />Two-year award - $120,000</p><p>Stephanie A. White, Ph.D.<br />University of California &#8211; Los Angeles, Los Angeles, CA<br /><i>Inside &amp; Outside the Critical Period: Neural Substrates for Vocal Learning</i><br />Two-year award - $120,000</p><p></td /><td width="95"></td> </td /> </tr /><tr></tr><td width="155" align="left" valign="top"></td> </td /> <td width="55"></td> </td /> <td width="505" align="left" valign="middle"></td> </td /> <td width="95"></td> </td /> </tr /><tr></tr><td width="155" align="left" valign="top"></td> </td /> <td width="55"></td> </td /></p>
ScienceAnna DunaevskyC. Susan CarterChandan J. VaidyaChristoph SchmitzDavid E. MandelbaumDavid L. PaulsDennis D.M. O'LearyFlavio KellerGillian BairdHugo TheoretJerzy WegielJudith K. GretherL. Alison McInnesLetitia R. NaiglesMartha R. HerbertNicholas PonzioOpal OusleyPh.D.Ph.D. & Lisa A. ParrPoul ThorsenPradeep G. BhideSchahram AkbarianStephanie A. WhiteYong-hui JiangGrantsGrantsFri, 06 May 2011 00:00:12 +0000pwhalen@gmail.com442 at https://www.autismspeaks.org2002 Grants Funded (CAN) https://www.autismspeaks.org/science/grants-program/research-we-have-funded/2002-grants-funded-can
Studies of a serotonin transporter (5HTT) mutation associates with Asperger's syndrome
<p><strong>Matthew Beckman, University of Alabama at Birmingham (Young Investigator)</strong><br />The search for genes associated with autism has been the focus of much attention by researchers in the past few years. Recently this search has led to the discovery of a mutation in the human serotonin transporter (SERT) coding sequence from patients with the following neuropsychiatric triad: Asperger's syndrome, obsessive-compulsive disorder, and anorexia. The function of a cloned serotonin transporter with this mutation (SERT-AS) has been characterized using [3H]5Ht uptake assays, binding assays employing a high affinity SERT ligand, ?-CIT, and immunocytochemical methods. When compared to the wild type SERT, mutant SERT-AS exhibits a roughly 1.5 fold increase in both maximum transporter velocity (Vmax) and binding sites (Bmax) and an increase in affinity (lower Kd) for ?-CIT, a high affinity ligand. Serotonin transporters have been shown to be highly regulated by various intracellular signal transduction pathways and direct phosphorylation of the transporter. Treatment of cells expressing the wild-type SERT with a nitric oxide donor S-Nitroso-N-acetylpenicillamine (SNAP) suggest a role for nitric oxide in the regulation of wild-type SERT, but the mutant SERT-AS is refractory to this stimulus. This work aims at characterizing the differences between the wild type SERT and the mutant SERT-AS using pharmacological, biochemical, and electrophysiological methods. Further, we hope to delineate the mechanism by which nitric oxide upregulates wild-type SERT with the goal of understanding why SERT-AS is constitutively upregulated. These studies offer the possibility for new insight into the pathogenesis and treatment of autism.</p>
fMRI of perceptual gating and response selction of high-functioning autism and in autism siblings
<p><strong>Matthew Belmonte, Cambridge University (Young Investigator)</strong><br />We propose to apply fMRI to ten-to-fourteen-year-old children with high-functioning autism or Asperger syndrome during performance of a visual attention task designed to factor out demands of perceptual selection from demands associated with response selection. Subjects will perform a two-stimulus colour-orientation discrimination in which different properties of each stimulus determine the status of the stimulus pair as a target or a non-target. In the stimulus in which orientation is the relevant property, colour will have to be suppressed, and in the stimulus in which colour is the relevant property, orientation will have to be suppressed. In a control task, both stimuli in each pair will be identical, and thus no suppression will be required. While both the experimental and the control tasks place demands on response selection, only the experimental task requires perceptual selection within each stimulus pair. We anticipate that perceptual selection will activate intraparietal sulcus, and that response selection will activate dorsolateral prefrontal cortex. We will compare results in autism to results in normal controls and also in autism siblings. The latter comparison is of interest since autism siblings share some of the cognitive characteristics of autism probands, yet they do not, in general, have autism. Siblings may thus offer a glimpse of the neurophysiological roots of the autistic syndrome, unobscured by later developmental sequelae.</p>
Functional characterization of the SPCH1 gene
<p><strong>Joseph Buxbaum, Mount Sinai School of Medicine (Pilot Research)</strong><br />A relationship has been postulated between certain language disorders and autism. The strongest evidence for this relationship is the identification of families with chromosomal abnormalities leading to language disorders in some family members and autism in others. Further support for this has been the genetic linkage of both language disorders and autism to a region of chromosome 7. Recently, a gene that underlies the language abnormality in a family with severe language disorder has been identified as foxp2. This gene is a transcription factor that has not been studied in detail. We and others are examining this gene as a candidate gene for autism, and we are also studying the expression of this gene during development. Given the importance of this gene, we here propose to disrupt this gene in mice (&quot;knockout&quot;) and thereby study its role in development of the central nervous system and identify genes that are regulated by foxp2.</p>
The Pre-school Social Communication Assessment Measure (PSCAM): Sensitivity to developmental change and early intervention efforts.
<p><strong>Tony Charman, Institute of Child Health (Psychometrics Award)</strong><br />Significant progress has been made in the identification of autism spectrum disorder (ASD) in the pre-school period. Age on entry to a program and an emphasis on developing communication skills are important elements of successful early intervention programs. Although several screening (CHAT, M-CHAT, STAT) and diagnostic instruments (ADI-R, ADOS-G) have good clinical utility, they are unlikely to be sensitive measures of intervention effectiveness. In part this is because their primary aim is diagnostic. Further, they focus on measuring impairments in social and communicative capacities. As most intervention programs have increasing social communicative competencies as a key aim, novel instruments that measure competencies in these early social communication abilities are required. Non-verbal social communication abilities including joint attention, imitation, play and reciprocal interactions are &quot;precursors&quot; to later language and social-communicative competence in both children with ASD and typical development. As part of screening and early intervention research studies over the past 8 years, we have assessed 50 children with ASD under the age of 24 months. We developed an interactive assessment measure that focuses on early social and communicative capacities (Pre-school Social Communication Assessment Measure; PSCAM). Systematic analysis of the PSCAM videotapes from the two extant datasets will allow us to evaluate if the PSCAM is a sensitive index of developmental change in pre-school children with ASD and a sensitive index of outcome in pre-school children with ASD enrolled in an ongoing early intervention study. <strong>Funded In partnership with Repligen Corporation</strong></p>
Identification of genes involved in autism
<p><strong>Russell Ferland, Beth Israel Deaconess Medical Center (Young Investigator)</strong><br />Autism is a neurological, developmental disorder that is characterized by abnormal communication and social interaction, and impaired cognitive development. Studies have demonstrated a clear genetic link with autism and have shown that it affects approximately 5:10000 people (Fombonne, 1999). Many groups have undertaken whole-genome screens in an effort to identify susceptibility loci in idiopathic autistic individuals living in the USA, with moderate success. Our laboratory has had great success in identify genes associated with neurological disorders through the use of families having consanguineous marriages from the Middle East. We are now applying this approach utilizing families with first-cousin marriages that have individuals affected with autism. We currently are examining families with first-cousin marriages in which approximately 25% of the children from these marriages have autism. We have conducted a genome-wide screen of these families and have demonstrated potential linkage to several loci in the genome. Our evidence suggests potential candidate regions on chromosomes 1, 3, 6, 8, 10, and 18 by multipoint analysis (multipoint LOD scores &gt; 1). Currently, we are attempting to test these candidate intervals through homozygosity mapping, marker analysis, and candidate gene identification in these chromosomal regions. Furthermore, our laboratory has initiated a collaboration with a school for autistic children in Kuwait and will obtain DNA from other consanguineous families with multiple autistic children, allowing us to expand our study of recessive autism genes. Overall, these studies aim to identify genes associated with autism, which potentially will lead to improved diagnosis and treatment.</p>
Studies of the relationship between autism and colonization of the intestinal tract by neurotoxigneic clostridial species
<p><strong>Sydney M. Finegold, M.D., University of California, Los Angeles, VA Medical Center (Bridge Grant)</strong><br />This group has been investigating the possibility that neurotoxin-producing bacteria could cause or significantly contribute to autistic symptoms in a subset of children with autism. Previous qualitative and quantitative analysis of stools indicated that there were differences between the stool flora of children with autism compared to that of control children. They are closing examining the Clostridium species isolated from the stools of children with autism. Using polymerase chain reaction (PCR) they will specifically test these isolates for the production of tetanus neurotoxin.</p>
Processing visual information in Autism. A pilot study
<p><strong>Dr. William Good, Smith-Kettlewell Eye Institute (Bridge Grant)</strong><br />Studies on autism have shown abnormalities in a number of vision-based functions such as visual attention, face recognition and visual search (e.g. Plaisted et.al., 1998, Jolliffe T, Baron-Cohen S, 1997, O'Riordan et.al., 2001). The results of these studies have been attributed to different high-level cognitive impairments. However, there is no data showing whether the low level processing of visual information is working normally in autism.</p><p>Most visual information is transmitted through the striate pathway (the pathway that originates in the retina and courses to the primary visual cortex, or V1, passing through the lateral geniculate nuclei). At V1 in the visual cortex, visual information is distributed into two main streams, dorsal and ventral. It is important to understand whether defects in V1 processing cause abnormalities in higher based visual functions (attention, face recognition, visual search).</p><p>The present study is designed to investigate low level and middle-level visual processing in order to study how local information about individual features is combined into more complex visual patterns. A better understanding of all levels of visual functioning in the autistic population will promote further research and help to interpret previous studies.</p>
To further develop several methods for reliable, quantitative, and reproducible measures of attention, and of implicit and explicit memory for individuals with autism
<p><strong>Barry Gordon, Johns Hopkins University School of Medicine (Psychometrics Award)</strong><br />Attention and memory (learning) are often impaired in individuals with autism, particularly in lower-functioning individuals. Problems with generalized attention (alertness), directed attention, explicit learning, and implicit learning have all been identified. Normally, many different tasks are used to measure these functions. However, valid measures of these underlying functions can be obtained through performance on two relatively simple tasks that such individuals can perform: stimulus-response association learning (both visual-visual and auditory-visual) and the sequential reaction time task (which requires only touching a target or touching a target predictively). Determination of these underlying abilities is certain to be enhanced when standard response recording is augmented by observations of response speed, posture, head position, and gaze direction. Accordingly, these tasks will be used in the current proposal, tailored to each individual's level of functioning. Training/testing will be done on a specialized computer system (Foundations), which automatically assigns materials, runs the tasks, and collects all data in a relational database format. Video monitoring will be done concurrently with task performance. A total of 20 subjects with autism will be tested (10 low-functioning, 10 high-functioning). Testing will be repeated at least once, in different physical surroundings and with different examiners, to test reliability. Validity will be established by construct and by comparison within- and across-subjects and across methods (e.g., manual response vs. gaze direction). These measures and methods are expected to be useful in detailed assessments of the components of attention and memory in large-scale clinical trials. <strong>Funded In partnership with Repligen Corporation</strong></p>
Toward generation of an autism mouse model by making locus-specific duplications homologous to human chromosomes 15q11-q13 region
<p><strong>Yong-hui Jiang, Baylor College of Medicine (Young Investigator)</strong><br />The numerous reports of autistic individuals with cytogenetic abnormalities of chromosome 15 have indicated that this region may harbor a susceptibility gene or genes for autistic disorder. The most common abnormalities are interstitial duplications and isodicentric chromosomes of exclusively maternal origin, suggesting that the gene or genes contributing to autism susceptibility may be subject to imprinting. Chromosome 15q11-q13 is an imprinted domain implicated in two neurological disorders, Prader-Willi syndrome (PWS) and Angelman syndrome (AS). Two maternally expressed genes, UBE3A and ATP10C, map within the region. UBE3A is the Angelman-causing gene and is expressed from the maternal allele in brain. We hypothesize that maternal duplication of 15q11-q13 may disrupt the normal expression of imprinted genes such as UBE3A and ATP10C and that abnormal expression of these two genes and/or others may contribute to autism susceptibility. We propose using the Cre-loxP system to prepare mutant mice with a duplication covering the entire 15q11-q13 region; a duplication covering the Ube3a gene and its possible regulatory elements; and a duplication covering the Atp10c gene. We will examine the expression pattern for Ube3a and do neuropathology, neurophysiology, and behavior testing on mutant mice to identify any impairment in morphology and social interaction. We believe there is a great likelihood that this will produce the first valid mouse model for autism. The mouse model will facilitate the genetic dissection of this trait and eventually lead to development of new and effective therapeutic interventions.</p>
The development of perceptual integration in autism
<p><strong>Chantal Kemner, University Medical Center Utrecht (Pilot Research)</strong><br />It is well known from clinical practice that subjects with autism are preoccupied with details, and they are usually found to excel in certain visuospatial tasks, which have in common that a tendency towards detail processing is advantageous. Extensive detail processing also seems to play a role in the social problems of autistics, such as face processing. Also, in autism structural as well as functional abnormalities are found in the occipital lobe. It is hypothesized that these findings indicate specific problems in early visual processing, viz. in visual perceptual integration. This is the ability to spatially integrate details of stimuli. An already funded study was started on perceptual integration in school age and adult autistic subjects. Two tasks are being used; one on texture segregation and one on face processing. During the tasks event-related brain potentials are measured, in order to get detailed information on the course of the perceptual integration process. However, there are indications that the abnormalities in autism are subjected to developmental influences. Therefore, it is warranted to study perceptual integration in autism as early as possible. In this project, the tasks will be presented to children with autism of about three years of age, who are recruited from a large screening study on early detection of autism in our department. The requested support will be used to accommodate the testing procedure for young children, to do the testing, and for analyzing the data.</p>
Sensory experience, behavioral therapy, and neural plasticity: Implications for autism remediation
<p><strong>Michael Kilgard, Ph.D., University of Texas at Dallas (Pilot Research)</strong><br />Autism is characterized by impairments in social interaction, disordered communication, repetitive behavior, and stereotyped interests. We propose that these symptoms lead to a form of isolation that disrupts the development of normal brain responses and in turn hinders the acquisition of critical language skills. Anatomical studies have established that even mild isolation during development can lead to significant weakening of cortical circuits. Although behavioral therapy and auditory training appear to improve language skills in autistic children. The neural basis of these improvements is not known. We have recently demonstrated that early sensory enrichment in rats leads to a profound increase in the sensitivity, frequency selectivity, response strength, and processing speed of neurons in primary auditory cortex. Similar brain plasticity may explain training-induced improvements of language function in autistic children. This proposal outlines experiments 1) to more completely characterize what specific aspects of an enriched environment strengthen cortical circuits, 2) to document how daily behavioral training improves cortical processing, 3) to establish the time course of developmental plasticity, and 4) to determine how dysfunction in the central cholinergic system affects auditory cortex maturation. Our preliminary findings indicate that during development cortical circuits are highly susceptible to degradation, and that targeted sensory enrichment can be extremely effective at restoring these circuits to normal performance. Results from the proposed experiments and others from the Autism Neural Plasticity Initiative will significantly influence the development of behavioral and pharmacological treatments for autism.</p>
An investigation of somatosensory processing in autistic children using magneto-encephalography (MEG)
<p><strong>David McGonigle, University of California, San Francisco (Young Investigator)<br /></strong>The social and communicative handicaps present in autistic individuals have led a number of researchers to suggest that autistic individuals can be best described as suffering from a deficit in 'theory of mind' (e.g. Boucher, 1989). Others have focused on autistics' disorders of 'executive function' (Russel, 1998). An alternative hypothesis is that the higher-order cognitive deficits observed in autism are caused by disorders of basic sensory processing. Frith (1989) has proposed that the disorders of perception arising in autism may result from weak 'central coherence' (CC), or an inability to extract global features or context from stimuli. To examine sensory processing in autistics, we propose to investigate the neuromagnetic correlates of the processing of somatosensory stimuli in autistic children using magnetoencephalography (MEG), a non-invasive neuroimaging method. We predict that autistic individuals will have disrupted spatial patterning in their primary somatosensory cortex (SI), and will furthermore show differences in amplitude of their somatosensory magnetic mismatch response when compared to age-matched controls. By quantifying and localizing the neural substrates of this aspect of autism (disorders in sensory processing), we believe our work may suggest novel therapeutic approaches (e.g. Merzenich et al., 1996) to the problem of autism in children.</p>
Using event-related potentials (ERP) to characterize auditory processing deficits in autism spectrum disorder and epilepsy
<p><strong>Elizabeth Pang, Ph.D., The Hospital for Sick Children Canada (Pilot Research)</strong><br />Autism Spectrum Disorder (ASD) is a childhood neuropathology affecting language, social interaction, behavior and play. Landau-Kleffner Syndrome (LKS) is an acquired epileptic aphasia where normal children develop a devastating loss, or regression, of language. Two important similarities exist between ASD and LKS: 1) over one-third of the children with ASD also report a language regression, and 2) both ASD and LKS manifest auditory processing deficits. The question raised whether ASD and LKS are biologically distinct entities or whether LKS is a later manifestation of regression seen along the spectrum of ASD. Examination of these auditory processing deficits may shed light on the pathoaetiology of these disorders. Auditory processing in the cerebral cortex can be examined using event-related potentials (ERP), in particular, the N1. Our ERP Lab has recently published the developmental N1 norms. Our feasibility studies suggest that a specific and consistent N1 abnormality can be observed and appeared over one cerebral hemisphere in ASD and over both hemispheres in LKS. This raises the possibility that the N1 abnormality may be a biological marker for ASD and LKS and that the pattern of appearance of this abnormality may be an important diagnostic toll for differentiating these disorders. Objectives: (1) Verify whether the N1 abnormality is a biological marker for ASD and LKS. (2) Test whether the N1 abnormality can discriminate ASD and LKS. (3) Look for other consistent abnormalities in the N1 related to ASD. (4) Test whether more complex auditory stimulii are better markers for these disorders.</p>
A pilot cross-cultural study of autism phenotypes in Puerto Rico
<p><strong>Jeremy Silverman, Mount Sinai School of Medicine (Pilot Research)</strong><br />The Mount Sinai Autism Family Studies Research Center recently studied a very large number of primarily non-Hispanic affected sibling pair families for genetic and phenotypic studies. In one study we identified several autism related clinical features that show evidence of familiality (i.e. the level of clinical expression among affected members in the same family are more likely to be similar than between unrelated affected individuals). Indeed, to date, we have looked at one of these features (phrase speech delay) and found substantially increased evidence for genetic linkage on chromosome 2 among affected sibships who share this characteristic. In the present pilot project we will recruit affected sibling pair families from Puerto Rico, a distinct population from the families previously studied, to begin to examine whether similar patterns of familiality are evident in affected sibling pair families in this culture as well. If so, the familiality of such features are more likely to be explained by similar underlying genetic factors as opposed to cultural/environmental ones. Blood samples too will be collected for our genetic studies and shared with AGRE, under the terms of our ongoing collaboration, and to examine lead levels in Puerto Ricans with autism. Puerto Rico is especially valuable as a separate recruitment site because the genetics of Puerto Rico is largely distinct from the U.S. mainland population and relatively homogeneous. In addition, families are frequently very large and highly cooperative, yet understudied despite the fact that Puerto Rican people constitute a major minority group in the United States.</p>
Provacative urine excretion of heavy metals using meso-2,3-dimercaptosuccinic acid (DMSA) in children with autism
<p><strong>Sarah E. Soden and Jennifer A. Lowry, Children's Mercy Hospitals &amp; Clinics (Bridge Grant)<br /></strong>The investigators propose measurement of urinary mercury, lead, cadmium, arsenic, and aluminum prior to and during a 24 hour provocative urine excretion study; comparing children with autism to non-autistic age matched controls. For the provoked excretion, we will use a heavy metal chelator meso-2,3-dimercaptosuccinic acid (DMSA). Our goals are to document difference that may exist between the two groups, to direct follow-up study, and to collect normative data for provocative urinary excretion of these environmental toxins.</p>
Cellular mechanisms controlling central oxytocinergic activity: Role in the pathophysiology of autism
<p><strong>Javier Stern, Wright State University (Pilot Research)</strong><br />Autism, a behavioral syndrome characterized by impairments in socialization, communication and stereotyped behaviors, has been the subject of substantial investigation. While major advances have been made, no pharmacological treatment has yet been found to consistently improve the symptoms or course of the disease. Developing a more effective treatment for autism requires research on the underlying pathophysiology. Even though autism is recognized as a neurodevelopmental syndrome, its neurobiological basis is poorly understood. Growing evidence indicates that the neuropeptide oxytocin plays an important role in social behavior, cognition and motor stereotypes. Furthermore, an abnormal function of oxytocinergic systems has been proposed to be involved in the pathogenesis of autism. Little is known about the cellular and functional properties of central oxytocin neuronal circuits, and how abnormal changes in these properties might be involved in the pathophysiology of autism. Using the oxytocin knock out mouse as an animal model for autism, we aim to determine a) the cellular mechanisms controlling neuronal excitability in oxytocin neurons that innervate limbic<br />structures involved in behavioral and social functions, b) the cellular mechanisms by which oxytocin modulates neuronal activity in these areas, and c) the mechanisms underlying altered neuronal function in limbic areas in the oxytocin knock out mouse. This work will provide fundamental information on the cellular mechanisms regulating central oxytocin activity. Furthermore, it will lead to a better understanding of the cellular mechanisms that contribute to the pathophysiology of autism, providing a basis for the development of therapeutic strategies for the treatment of this disease.</p>
Mechanisms underlying receptors delivery to synapses in early postnatal development
<p><strong>Takuya Takahashi, Cold Spring Harbor Laboratory (Young Investigator)</strong><br />Large deficits in information processing such as learning and memory have been found in autistic patients. It is suggested that disruption of the glutamatergic neurons is responsible for these deficits. Long-term potentiation (LTP), the long lasting enhancement of synaptic strength induced by repetitive activation of glutamatergic excitatroy synapse, is believed to have important roles in learning and memory. One possible mechanism of LTP expression is the rapid delivery of the functional AMPA-type glutamate receptors to synapses from non-synaptic sites. Indeed, GFP-tagged AMPA receptor 1 (GluR1) is delivered to synapses after LTP-inducing stimuli. In contrast, GluR2 is continuously delivered to synapses and replaces existing synaptic receptors. Signaling mechanism of synaptic delivery of AMPA receptos is porrly understood. Interestingly, GluR4 is expressed exclusively in the first postnatal week and delivered to synapses by spontaneous activity. This suggests that GluR4 has a crucial role in information processing during early postnatal development. Considering the early onset of autism, it is important to understand the cellular and molecular mechanism of infomration processing during early postnatal development. We have characterized the important region for delivery in the carboxyl terminus of GluR4 and isolated Hsc70 as a binding protein of this region. We will analyze the functional role of Hsc70 on the delivery of GluR4.</p>
To assess a total of 35 SNPs (single-nucleotide polymorphisms) in 6 to 10 positional candidate genes using a complete set of DNA from well-characterized families with autism spectrum disorders from the AGRE family collection of biomaterials.
<p><strong>Rudolph Tanzi, Massachusetts General Hospital (Contracted Research)</strong><br />Autism and autism spectrum disorders are genetically complex neuropsychiatric disorders of early life. To date, several whole genome scans on independent samples were performed indicating the existence of numerous putative autism loci across different chromosomes. One of the most recent studies was performed by the Autism Genetic Resource Exchange (AGRE) Consortium and yielded suggestive linkage evidence on at least four chromosomes (i.e. chromosomes 5, 8, 19 and X; Lui et al., 2001). In addition, using different analytic methods and additional markers other investigators were able to show linkage to other loci in the same sample (e.g. Buxbaum et al., 2001). Our study aims at assessing a total of 35 SNPs (single-nucleotide polymorphisms) in 6 to 10 positional candidate genes in these regions in the AGRE dataset. Specifically, we will use high-throughput fluorescence-polarisation single-base extension (FP-SBE) detection for genotyping of 3 to 5 SNPs per gene, which will then be analyzed either individually using the family-based association test program (FBAT), or as multi-locus haplotypes using TRANSMIT. Both programs allow to estimate valid significance values even in the presence of known linkage - as is the case here, with positive results from the prior genome scans - while making full use of all the available genotype information. Our laboratory has extensive experience will all aspects of high-throughput SNP genotyping and analysis, which can be directly applied to the AGRE sample. These efforts to identify new genetic risk factors will, together with the contributions of the other AGRE Consortium members, help to unravel the genetics of this appalling disorder.</p>
Analysis of candidate genes in autism
<p><strong>Enrique Villacres, University of Washington (Pilot Research)</strong><br />Current evidence suggests that autism is a polygenic disorder with at least five or more genes causing the disease. We hypothesize that chromosomal translocations found in some autistic patients cause or contribute to autism. The genes disrupted by these translocations are candidate genes for autism. These genes may be major effect loci coincident with chromosomal regions identified by linkage analysis or minor effect loci not detectable by standard family-based methods. Point mutations or polymorphisms in the genes identified may contribute to autism in subjects with normal karyotype. We have performed molecular analysis of a balanced chromosomal translocation t(7;20) (q11.2; p11.2) in a pair of twins with autism. Specifically, we have identified a novel gene (AUTS2) at 7q11.2, that spans this breakpoint. Two recent searches for susceptibility loci in autism using genetic linkage methods yielded positive evidence for an autism locus on chromosome 7q (Barret et al., 1999; IMGSAC, 2001). AUTS2 is expressed in fetal brain, suggesting that alterations in this gene could result in abnormal development leading to autism. Preliminary evidence does not support allelic association with autism with only two SNPs studied. The goals of this proposal are to 1) identify the chromosome 20 gene/genes disrupted by t(7;20) in the monozygotic autistic twins; 2) identify genes disrupted by all the breakpoints in an autistic boy with a complex rearrangement t(1;7;21); and 3) screen translocation breakpoint genes for mutations in non-breakpoint subjects. Finding one or more genetic cause of autism will provide clues to the treatment of this disorder.</p>
Pilot pediatric diagnostic study for autism and other developmental problems
<p><strong>Stuart Shanker, Ph.D. and Stanley Greenspan, M.D., York University (Contracted Research)</strong><br />There is great interest in identifying children at risk of developing Autism Spectrum Disorder (ASD) at earlier ages in order to enhance the opportunity for early intervention as well as to understand the early stages of this disorder in the context of the search for neurobiological correlates and preventative strategies. Recent research suggest that an early sign of the developmental trajectory leading to ASD is a deficit that appears in infants around the age of 9 months in their capacity for reciprocal exchanges of emotional expressions. In these exchanges of affect, and impairment can also be observed in the detail and complexity of the facial expressions of emotion, as well as a discord between the infant's movements in response to her caregiver's vocalizations, facial expressions, and gestures. This study proposes to develop a systematic procedure for looking at the dynamic process of co-regulated facial expressions of affect and the rhythmicity of the infant's movements as a tool for identifying 9 month-old infants that are at risk of developing ASD.</p>
ScienceBarry GordonChantal KemnerDavid McGonigleDr. William GoodElizabeth PangEnrique VillacresJavier SternJeremy SilvermanJoseph BuxbaumMatthew BeckmanMatthew BelmonteMichael KilgardPh.D.Rudolph TanziRussell FerlandSarah E. Soden and Jennifer A. LowryStuart ShankerSydney M. FinegoldTakuya TakahashiTony CharmanYong-hui JiangGrantsGrantsThu, 05 May 2011 23:28:50 +0000pwhalen@gmail.com441 at https://www.autismspeaks.org2003 Research Awards (NAAR)https://www.autismspeaks.org/science/grants-program/research-we-have-funded/2003-research-awards-naar
<p>In 2003, NAAR committed approximately $4.9 million to fund 35 pilot studies, 13 pre- and post-doctoral fellowships and two autism training programs. NAAR's 2003 research commitments funded autism investigations in the U.S., Canada, England, Scotland and Denmark. As part of the 2003 awards, NAAR is co-sponsoring two autism training programs in partnership with the Canadian Institute of Neurosciences, Mental Health and Addiction.<br /></p><p><b>
<b>2003 PILOT STUDY GRANTS</b>
</b></p><p>Susan Birren, Ph.D. <br />Brandeis University, Waltham, MA<br /><i>Regulation of Cortical Synaptogenesis by Basal Forebrain Cholinergic Neurons</i><br />Two-year award - $120,000<br />Research Partner: Richard and Susan Smith Family Foundation</p><p>Patrick Bolton, Ph.D.<br />The Institute of Psychiatry at King's College, London, England<br /><i>Speech &amp; Language Impairments and Autism Spectrum Disorders: A Twin Study of the Links<br /></i>Two-year award - $119,083</p><p>Patrick Bolton, Ph.D.<br />The Institute of Psychiatry at King's College, London, England<br /><i>Event Related Potential &amp; Behavioral Investigations of Face Processing in Individuals with Tuberous Sclerosis and Autism</i><br />Two-year award - $113,011</p><p>Kenneth Campbell, Ph.D.<br />Children's Hospital Research Foundation, Cincinnati, OH<br /><i>Genetic Control of Mammalian Amygdalar Development</i><br />Two-year award - $120,000</p><p>Alice Carter, Ph.D.<br />University of Massachusetts, Boston, MA<br /><i>Maternal Sensitivity, Joint Attention and Gains in Language Acquisition in Toddlers Diagnosed with Autism</i><br />Two-year award - $103,096</p><p>Manuel Casanova, M.D.<br /><place w:st="on" /><placetype w:st="on" />University</placetype /> of <placename w:st="on" />Louisville</placename /></place />, <placename w:st="on" />Louisville</placename />, KY<br /><i>Macroscopic Correlates of Minicolumnar Abnormalities in Autism</i><br />Two-year award - $120,000<br />Research Partner: Nancy Lurie Marks Family Foundation</p><p>Susan Christian, Ph.D.<br />University of Chicago, Chicago, IL<br /><i>Identifying Small Chromosomal Rearrangements in Autism Using Microarrays</i><br />Two-year award - $118,845<br />Research Partner: Autism Coalition for Research &amp; Education and Solving the Mystery of Autism</p><p>Antonio Convit, M.D.<br />New York University School of Medicine, New York, NY<br /><i>Social Cognition and Brain Volumes in Asperger Syndrome</i><br />Two-year award - $112,900</p><p>Thomas Cook, Ph.D.<br />Rutgers University, Piscataway, NJ<br /><i>Placental Metabolism &amp; Fatty Acid Homeostasis in Fetal Imprinting of Autism and Autism Spectrum Disorders</i><br />Two-year award - $120,000</p><p>Michael Cuccaro, Ph.D.<br />Duke University Medical Center, Durham, NC<br /><i>Retrospective Association Analysis of Children with Idiopathic Autism Spectrum Disorders Treated with Fluoxetine</i><br />Two-year award - $109,703<br />Research Partner: The Michael &amp; Cynthia Moran Family &amp; Friends</p><p>Mirella Dapretto, Ph.D.<br />University of California at Los Angeles, Los Angeles, CA<br /><i>Language &amp; Prosody in Autism: Evidence from fMRI</i><br />Two-year award - $120,000</p><p>Michelle Dunn, Ph.D.<br />Albert Einstein College of Medicine, Bronx, NY<br /><i>Understanding Cortical Auditory Processing Abnormalities in Children with Autism</i><br />Two-year award - $119,912<br />Research Partner: Nancy Lurie Marks Family Foundation</p><p>Michelle Dunn, Ph.D.<br />Albert Einstein College of Medicine, Bronx, NY<br /><i>Mapping Lexical Organization in Children with Autism</i><br />Two-year award - $119,912</p><p>Nicole Gage, Ph.D.<br />University of California at Irvine, Irvine, CA<br /><i>MEG Investigations of Cortical Auditory Processing in Children with Autism</i><br />Two-year award - $109,788</p><p>H. Hill Goldsmith, Ph.D.<br />University of Wisconsin at Madison, Madison, WI<br /><i>A Birth Register-based Twin Study of Autism Spectrum Disorders</i><br />Two-year award - $118,910</p><p>Eli Hatchwell, Ph.D.<br />Cold Spring Harbor Laboratory, Cold Spring Harbor, NY<br /><i>Genomic Copy Number Variation in Autism</i><br />One-year award - $60,000</p><p>Karl Herrup, Ph.D.<br />Case Western Reserve University, Cleveland, OH<br /><i>The Engrailed-2 Mutant as a Model of the Neuropathology of Autism</i><br />Two-year award - $120,000<br />Research Partner: Autism Coalition for Research and Education</p><p>Laura Hewitson, Ph.D.<br />University of Pittsburgh, Pittsburgh, PA<br /><i>Autism in Primates: Genetics vs Environment</i><br />Two-year award - $118,825</p><p>Jana Iverson, Ph.D.<br />University of Pittsburgh, Pittsburgh, PA<br /><i>Early Identification of Autism: A Prospective Study</i><br />Two-year award - $119,861</p><p>Russell Margolis, M.D.<br />Johns Hopkins School of Medicine, Baltimore, MD<br /><i>Genetic Mutations Associated with Autism in Unexplored Regions of FOXP2</i><br />One-year award - $56,063</p><p>James Millonig, Ph.D.<br />University of Medicine &amp; Dentistry of New Jersey/Robert Wood Johnson Medical School, Piscataway, NJ<br /><i>Studying Mouse Cerebellar Development as a Tool to Identify Autism Susceptibility Genes</i> <br />Two-year award - $120,000<br />Research Partner: Autism Coalition for Research and Education</p><p>Sherie Novotny, M.D.<br />University of Medicine &amp; Dentistry of New Jersey/Robert Wood Johnson Medical School, Piscataway, NJ<br /><i>Galantamine vs Placebo in Childhood &amp; Adolescent Autism</i><br />Two-year award - $118,526</p><p>Payam Rezaie, Ph.D.<br />The Open University, Milton Keynes, England<br /><i>Assessment of the Glial Response Within the Cerebral Cortex in Autism</i><br />Two-year award - $119,973</p><p>Timothy Roberts, Ph.D.<br />University of Toronto, Toronto, Ontario<br /><i>MEG Correlates of Linguistic Processing at and Below the Word Level in Autism</i><br />Two-year award - $119,918<br />Research Partner: Nancy Lurie Marks Family Foundation</p><p>Peter Scheiffele, Ph.D.<br />Columbia University, New York, NY<br /><i>Frequency &amp; Functional Characterization of Neuroligin Mutations</i><br />Two-year award - $119,998</p><p>Stephen Sheinkopf, Ph.D.<br />Brown Medical School, Providence, RI<br /><i>Vagal Tone &amp; Social Behaviors in Children with Autistic Disorder</i><br />Two-year award - $116,952</p><p>Elise Temple, Ph.D.<br />Cornell University, Ithaca, NY<br /><i>Neural Mechanisms Underlying &quot;Theory of Mind&quot;: fMRI Studies of Normally Developing and Autistic Children</i><br />Two-year award - $112,916</p><p>Poul Thorsen, M.D., Ph.D.<br />NANEA at Department of Epidemiology and Social Medicine/Aarhus University, Denmark<br /><i>Exposure to Pharmaceuticals in Pregnancy &amp; Development of Autistic Disorder</i><br />Two-year award - $118,454<br />Research Partner: Autism Coalition for Research and Education</p><p>Jochen Triesch, Ph.D.<br />University of California at San Diego, La Jolla, CA<br /><i>The MESA Project: Modeling the Emergence of Shared Attention</i><br />Two-year award - $120,000</p><p>Michael Ullman, Ph.D.<br />Georgetown University, Washington, DC<br /><i>Neurocognitive Correlates of Language in Autism</i><br />Two-year award - $118,575</p><p>John Welsh, Ph.D.<br />Oregon Health &amp; Science University, Portland, OR<br /><i>Inferior Olive &amp; Autism: Electrical Synapses, Neuronal Synchrony &amp; Cognition</i><br />Two-year award - $101,639<br />Research Partner: Nancy Lurie Marks Family Foundation</p><p>Justin Williams, M.B.B.S., MSc<br />University of Aberdeen, Aberdeen, England<br /><i>Functional Neuroimaging Studies of Action, Facial and Object-directed Imitation</i><br />Two-year award - $119,977</p><p>Peter Zandi, Ph.D.<br />Johns Hopkins School of Public Health, Baltimore, MD<br /><i>Maternal-fetal Incompatibility and Autism Risk</i><br />One-year award - $59,998</p><p>Xiaoxi Zhuang, Ph.D.<br />University of Chicago, Chicago, IL<br /><i>Behavioral Effects of Hyper- and Hypo-Serotonergic Function in Transgenic Mouse Models</i> <br />Two-year award - $120,000</p><p>Lonnie Zwaigenbaum, M.D.<br />McMaster University, Hamilton, Ontario<br /><i>Investigating the Emergence of Familial Traits in Autism</i><br />Two-year award - $120,000<br />Research Partner: Dan Marino Foundation</p>
ScienceAlbert Einstein CoAlice CarterAntonio ConvitAutism Coalition for Research & Education and Solving the Mystery of AutismBostonBrandeis UniversityCAChicagoChildren's Hospital Research FoundationCincinnatiDuke University Medical CenterDurhamEnglandILKenneth CampbellLondonLos AngelesLouisvilleMAManuel CasanovaMichael CuccaroMichelle DunnMirella DaprettoNancy Lurie Marks Family FoundationNCNew YorkNew York University School of MedicineNJNYOHPatrick BoltonPh.D.PiscatawayRichard and Susan Smith Family FoundationRutgers UniversitySusan BirrenSusan ChristianThe Institute of Psychiatry at King's CollegeThe Michael & Cynthia Moran Family & FriendsThomas CookUniversity of California at Los AngelesUniversity of ChicagoUniversity of LouisvilleUniversity of MassachusettsWalthamGrantsGrantsThu, 05 May 2011 18:33:43 +0000pwhalen@gmail.com429 at https://www.autismspeaks.org2004 Research and Fellowship Awards (NAAR)https://www.autismspeaks.org/science/grants-program/research-we-have-funded/2004-research-and-fellowship-awards-naar
Research Funded: 2004
<p>In 2004, NAAR committed $6.2 million to fund 25 pilot studies, 14 pre- and post-doctoral fellowships as well as two large collaborative programs: the NAAR Autism Genome Project and expansion of the Autism Tissue Program. In addition, NAAR's 2004 research commitments include the ongoing support of two interdisciplinary autism training programs that are being co-sponsored by the Canadian Institutes of Health Research. NAAR's 2004 research awards are the largest single-year commitment to biomedical autism research ever made by a non-governmental organization and are funding pilot studies and fellowships in the U.S., Canada and England.<br /></p><p><b>
<b>Collaborative Projects &amp; Programs</b>
</b></p><p><b><a href="/inthenews/naar_archive/largest_autism_genetics.php">NAAR Autism Genome Project</a></b> <br />In 2004, NAAR has committed $2 million towards the NAAR Autism Genome Project, an NIH partnership that is the largest research collaboration ever to focus on the genetics of the disorder. The NAAR Autism Genome Project will map the human genome in the search for autism susceptibility genes - the genes responsible for the inherited risk for autism. A public/private research partnership, this collaboration includes approximately 170 of the world's leading genetic researchers from 50 academic and research institutions that have pooled their DNA samples in a collaborative effort.</p><p><b><a href="/science/programs/atp/index.php">Autism Tissue Program</a></b><a href="/research/atp.htm"></a><br />NAAR has committed $200,000 in 2004 towards the ongoing expansion of the Autism Tissue Program, a parent-led brain tissue donation program dedicated to autism research and jointly supported by the NIH. The program makes post-mortem brain tissue available to as many qualified scientists as possible who are focused on autism research. NAAR established and first funded the Autism Tissue Program in 1998.</p><p><b>
<b>2004 Research and Fellowship Awards</b><br />
</b></p><p>Arthur Beaudet, Ph.D.<br />Baylor College of Medicine, Houston, TX<br /><i>Search for an Autism Gene on the Y Chromosome</i><br />Two-Year Award- $120,000<br /><font size="2" face="Arial">
Research Partner: Nancy Lurie Marks Foundation
</font><br /></p><p>Benjamin Cheyette, Ph.D.<br />University of California, San Francisco, San Francisco, CA<br /><i>Neural Development and Function of DPR genes</i><br />Two-Year Award- $118,494</p><p>Davide Comoletti, Ph.D.<br />University of California, San Diego, San Diego, CA<br /><i>Neuroligin and Autism Spectrum Disorder: Role of R451C Mutation in Neuroligin-3</i><br />Two-Year Award- $120,000</p><p>Lisa Croen, Ph.D.<br />Kaiser Permante - Division of Research, Oakland, CA<br /><i>Biologic Markers of Maternal Infection and Immune Function in Autism</i><br />Two-Year Award- $119,680</p><p>Karen Dobkins, Ph.D.<br />University Of California, San Diego, San Diego, CA<br /><i>Neural and Behavioral Precursors to Autism in Infancy</i><br />Two-Year Award- $69,942 <br /></p><p>Jonathan Freedman, Ph.D.<br />Duke University, Durham, NC<br /><i>Double Hit Hypothesis of Autism: Susceptibility and Environmental Exposure to Metals</i><br />Two-Year Award - $120,000<br />Research Partner: The Forlenza Family in Loving Memory of Constance and Vincent Forlenza</p><p>J. Jay Gargus, Ph.D.<br />University of California, Irvine, Irvine, CA<br /><i>Energy-deficient Metabolic Phenotype in Subgroups of Autism</i><br />Two-Year Award- $120,000</p><p>Samie Jaffrey, Ph.D.<br />Weill Medical College of Cornell University, Ithaca, NY<br /><i>Analysis of Synaptogenesis Signal Transduction Pathways that are Defective in Autism<br />Spectrum Disorders</i><br />Two-Year Award- $99,000</p><p>Boutheina Jemel, Ph.D.<br />Riviere des Prairies Hospital, Fernand Seguin Research Center, Montreal, Canada<br /><i>Top-Down Mechanisms on Visual Perception in Autism: An Event-related Brain Potential Investigation</i> <br />Two-Year Award- $104,820</p><p>Robert Joseph, Ph.D.<br />Boston University School of Medicine, Boston, MA<br /><i>Neurobiological Markers of Language Acquisition and Functioning in Autism</i><br />Two-Year Award- $117,075<br /><font size="2" face="Arial">
Research Partner: Nancy Lurie Marks Foundation
</font></p><p>Ami Klin, Ph.D.<br />Yale Child Study Center, New Haven, CT<br /><i>Listening Preferences in Toddlers with Autism: The Playtest as an Early Screening Device</i><br />Two-Year Award- $120,000</p><p>Kenneth Kosik, M.D.<br />Brigham and Women's Hospital, Boston, MA<br /><i>A Molecular Pathway Leading to Autism</i><br />Two-Year Award- $100,000<br />
Research Partner: John LeClaire and Ruth Hodges, in honor of the golden wedding anniversary of Robert and Elizabeth LeClaire
</p><p>Dominic Massaro, Ph.D.<br />University of California, Santa Cruz, Santa Cruz, CA<br /><i>Multisensory Integration by Children with Autism</i><br />Two-Year Award- $113,712</p><p>Daniel Messinger, Ph.D.<br />University of Miami, Miami, FL<br /><i>Developing Deficits in Infant Siblings of Children with ASD: Emotional Communication<br />And Psychophysiological Functioning</i><br />Two-Year Award- $105,891</p><p>Stewart Mostofsky, Ph.D.<br />Kennedy Krieger Institute, John Hopkins School of Medicine, Baltimore, MD<br /><i>Dependent Motor Learning in Autism Examination of Visual and Somatosensory</i><br />Two-Year Award- $117,019<br /><font size="2" face="Arial">
Research Partner: Nancy Lurie Marks Foundation
</font></p><p>Ruth Nass, Ph.D<br />NYU Medical Center, New York City, NY<br /><i>Frequency and Pathophysiology of Autistic Spectrum Disorders in Children with<br />Tuberous Sclerosis Complex</i><br />Two-Year Award- $53,359</p><p>Julia Noland, Ph.D.<br />Vanderbilt University, Nashville, TN<br /><i>Cognitive Control in the First Year of Life in Siblings of Children with Autism Spectrum Disorders</i><br />Two-Year Award- $111,670</p><p>Peter Penzes, Ph.D<br />Northwestern University, Feinberg School of Medicine, Chicago, IL<br /><i>Regulation of Structural Plasticity of Excitatory Synapses</i><br />Two-Year Award- $120,000</p><p>Elizabeth Powell, Ph.D.<br />University of Maryland, Baltimore, Baltimore, MD<br /><i>Regulation of Interneuron Proliferation</i><br />Two-Year Award- $119,152</p><p>Opal Ousley, Ph.D.<br />Emory University School of Medicine, Atlanta, Georgia<br /><i>Assessing Functional and Anatomical Connectivity in Autism</i><br />Two-Year Award- $120,000</p><p>Howard Ring, Ph.D.<br />University of Cambridge, Cambridge, England<br /><i>Testing the N400 as a Marker for Optimizing Information Presentation to People with Autism</i><br />Two-Year Award- $103,865</p><p>Sally Rogers, Ph.D.<br />University of California, Davis, Davis, CA<br /><i>Neonatal Social Responses of Infant Siblings</i><br />Two-Year Award - $76,956</p><p>Trilochan Sahoo, Ph.D.<br />Baylor College of Medicine. Houston, TX<br /><i>Development of a Genomic Microarray for Detecting Chromosomal Abnormalities in<br />Autism Spectrum Disorders</i><br />Two-Year Award- $117,590</p><p>Anne Sereno, Ph.D<br />University of Texas, Houston Health Science Center, Houston, TX<br /><i>The Neurobiology of Social Visual Pursuit: Implications for Autism</i><br />Two-Year Award- $120,000</p><p>Linda Watson, Ph.D.<br />University of North Carolina at Chapel Hill, Chapel Hill, NC<br /><i>Auditory Orienting and Language Outcomes in Children with Autism</i><br />Two-Year Award $115,338</p><p>Pre-Doctoral Fellowships</p><p>IWWK Health Centre/ Dalhousie University<br />Halifax, Nova Scotia<br />Mentor: Susan Bryson, Ph.D.<br />Fellow: Irene Drmic<br /><i>Discriminative Validity and Physiological Correlates of Impaired Disengagement in Autism</i></p><p>University of Massachusetts <br />Boston, MA<br />Mentor: Alice Carter, Ph.D.<br />Fellow: Elizabeth A. Mongillo<br /><i>Social-cognitive Processing in Infant Siblings of Children with Autism<br /></i><font size="2" face="Arial">
Research Partner: John LeClaire and Ruth Hodges, in honor of the golden wedding anniversary of Robert and Elizabeth LeClaire
</font></p><p>University of Medicine and Dentistry of New Jersey/ <br />Robert Wood Johnson Medical School<br />Piscataway, NJ<br />Mentor: James Millonig, Ph.D.<br />Fellow: Rym Beynard<br /><i>Genetic Analysis of the Homeobox Transcription factor ENGRAILED2 in autism spectrum disorder</i></p><p>Princeton University<br />Princeton, NJ<br />Mentor: James Haxby, Ph.D.<br />Fellow: Kimberly Montgomery<br /><i>Investigations of the Mirror Neuron System in Autism</i></p><p>University of Pittsburgh<br />Pittsburgh, PA<br />Mentor: Mark Strauss, Ph.D.<br />Fellow: Holly Zajec Gastgeb<br /><i>Concept Abstraction and Face Recognition in Individuals with Autism</i></p><p>Carnegie Mellon University and Center for Excellence in Autism Research<br />Pittsburgh, PA<br />Mentor: Marlene Behrmann, Ph.D.<br />Fellow: Cibu Thomas<br /><i>Integration of Information and Functional Brain Connectivity in Autism</i></p><p>Birkbeck College, University of London<br />London, England<br />Mentor: Gergely Csibra. Ph.D.<br />Fellow: Karla Holmboe<br /><i>Development of Early Prefrontal Functioning in Autism</i></p><p>Post-Doctoral Fellowships</p><p>Newcomen Centre<br />London, England<br />Mentor: Gillian Baird, Ph.D.<br />Fellow: Nick Riches, Ph.D.<br /><i>Investigating the Biomedical and Psychological Characteristics of Children with ASD, focusing on of Language and Communication</i></p><p>Carnegie Mellon University and Center for Excellence in Autism Research<br />Pittsburgh, PA<br />Mentor: Marlene Behrmann, Ph.D.<br />Fellow: Kate Humphreys, Ph.D.<br /><i>Face Processing in Infant Siblings of Children with Autism</i></p><p>Albert Einstein College of Medicine<br />New York, NY<br />Mentor: Isabelle Rapin, M.D.<br />Fellow: Sylvie Goldman, M.D.<br /><i>Stereotypies in Autism and Other Developmental Disorders as a Function of Age, IQ, and Severity of the Disorder</i></p><p>University of California, San Francisco<br />San Francisco, CA<br />Mentor: John L.R. Rubenstein, M.D., Ph.D.<br />Fellow: Maria Inmaculada Cobos-Sillero, Ph.D.<br /><i>Regulation of Cortical GABAergic Neuronal Development and Function by the DLX family of Transcription Factors</i></p><p>University of Pittsburgh School of Medicine<br />Pittsburgh, PA<br />Mentor: Beatriz Luna, Ph.D. <br />Fellow: Kathryn Suzanne Scherf, Ph.D.<br /><i>The Emergence of Object-processing Deficits in Autism: A Brain-based Investigation</i></p><p>John Hopkins School of Medicine<br />Balitmore, MD<br />Mentor: Alex Kolodkin, Ph.D.<br />Fellow: Qiaung Wang, Ph.D.<br /><i>Regulation of Dendritic Morphology</i></p><p>Yale Child Study Center<br />New Haven, CT<br />Mentor: Robert Schultz, Ph.D.<br />Fellow: Marc Thioux, Ph.D.<br /><i>MRI Studies of the Neurophysiological Bases of Autism Spectrum Disorders</i></p>
ScienceAmi KlinArthur BeaudetBaylor College of MedicineBenjamin CheyetteBostonCA Karen DobkinsCA Lisa CroenCA Samie JaffreyCanadaCTDavide ComolettiDominic MassaroDurhamFernand Seguin Research CenterHoustonIrvineIthacaJ. Jay GargusJonathan FreedmanKenneth KosikM.D. Brigham and Women's HospitalMA John LeClaire and Ruth HodgesMontrealNancy Lurie Marks FoundationNC The Forlenza Family in Loving Memory of Constance and Vincent ForlenzaNew HavenNY Boutheina JemelOaklandPh.D.Ph.D. Boston University School of MedicinePh.D. Duke UniversityPh.D. Kaiser Permante - Division of ResearchPh.D. Riviere des Prairies HospitalPh.D. University of CaliforniaPh.D. Weill Medical College of Cornell UniversityPh.D. Yale Child Study CenterRobert JosephSan DiegoSantSanta CruzTX Nancy Lurie Marks FoundationGrantsGrantsWed, 04 May 2011 23:33:21 +0000pwhalen@gmail.com415 at https://www.autismspeaks.org2003 Grants Funded (CAN) https://www.autismspeaks.org/science/grants-program/research-we-have-funded/2003-grants-funded-can
Synaptogenesis and chromosomal rearrangements in autism
<p><strong>Thomas Bourgeron, Ph. D., Pasteur Institute (Pilot Project)<br /></strong>Autism is a developmental disorder characterized by impaired social interaction and communication, in addition to restricted range of interests and activities. The PARIS study, an international collaborative project coordinated by Pr. Marion Leboyer (Paris) and Pr. Christopher Gillberg (Goteborg), joined the efforts of clinicians in Europe and the United States with the purpose of gathering a large population of autistic sib pairs and trios to perform linkage and association analyses. During the systematic mutation screening and chromosomal analysis of autistic subjects, we identified mutations in cell adhesion molecules involved in synaptogenesis and chromosomal rearrangements associated with autism and Asperger syndrome. Synaptogenesis, the formation of functional synapses, is considered as the final step in the development of the central nervous system. Among the genes involved in this process, cell adhesion molecules are crucial factors for the identification of the appropriate partner cell. On the basis of these results, this project aims to analyze cell adhesion molecules involved in synaptogenesis and to identify the genes localized at or near the breakpoints of chromosomal translocations. For this, we will screen for mutations in candidate genes by direct sequencing and characterize translocated genes using Fluorescent In situ Hybridization (FISH). When disrupted genes will be identified, they will be systematically screened in all autistic subjects recruited by the PARIS study. In parallel, functional analysis of the mutations identified in the autistic subjects will be conducted to understand their biological roles and to evaluate the consequence of these mutations in the establishment of the neural connection pattern.</p>
The neural development of motion perception in high-functioning children with autism
<p><strong>Elizabeth a. Hoffman, Ph.D., Georgetown University Medical School (Young Investigator)</strong><br />In addition to the hallmark deficit of social communication, individuals with autism exhibit visual motion processing abnormalities. Despite the prevalence of this profile of dysfunction, there are no reports of brain changes associated with motion perception deficits and few studies have investigated the neurophysiology of impaired social perception in autistic individuals. Furthermore, the link between these two classes of impairment has not been established, although researchers have suggested that the ability to interpret motion cues may be necessary for later development of social communication. Neuroimaging studies have localized motion perception in normal adults to a region in the middle temporal lobe, area V5/MT. We will use functional magnetic resonance imaging (fMRI) to probe the motion system in typically developing and autistic children, ages 8-10 years. Subjects will view dynamic and static arrays of cartoon fish. In the dynamic condition, a proportion of the fish will &quot;swim&quot; coherently in one direction, with the remaining fish moving randomly. Subjects will determine whether or not two sequential arrays of fish are moving in the same direction. Subjects will view arrays of still fish in the static condition. This project will address the following questions: [1] what is the neural representation of motion perception in normal children? [2] How does this representation differ in age-matched individuals with autism? [3] Can we identify a neural network that compensates for a dysfunctional motion perception system?</p><p>First year funding partner: The Autism Coalition for Research and Education</p>
Candidate Genes for Autism on Chromosome 7q
<p><strong>AHM Mahbubul Huq, M.D., Ph.D., Wayne State University (Pilot Project)</strong><br />Several genome screens found evidence of linkage for autism on overlapping regions on chromosome 7q. The broad goal of this proposal is to identify autism susceptibility gene or genes on chromosome 7q. The hypothesis underlying this proposal is that common variants (&gt;5% frequency) underlie susceptibility to autism. Our approach is direct analysis of the likely candidate genes and single nucleotide polymorphism (SNP)-based linkage disequilibrium mapping using a large sample of families with autism. We have selected 30 candidate genes from consensus regions of linkage based on known or presumed function and expression in brain. We will sequence exons and promoters of these genes in 20 individuals with autism to identify variants that rare in general population but are enriched in autism population. SNPs will also be selected from the databases focusing on coding sequence and promoter variants. We will perform multilocus linkage disequilibrium and haplotype analyses of the SNPs in the candidate genes. In order to improve our chance of identifying susceptibility alleles, we will also perform quantitative trait association studies of the candidate genes. We will genotype enough SNPs in the candidate genes to capture the common haplotypes. The genes that we have selected are less than 50 kb in size; so 10 SNPs in each gene will capture the most common haplotypes. There is an ongoing debate whether &quot;few common variants&quot; or &quot;multiple rare variants&quot; underlie susceptibility to complex traits. With our strategy and sample size, we will able to identify susceptibility alleles with frequency greater than 5%.</p>
Auditory and visual Processing Deficits in Autism
<p><strong>Tal Kenet, Ph.D., University of California, San Francisco (Young Investigator)</strong><br />We believe one of the core weaknesses in autism is a general failure in gain control mechanisms. Such a failure would be manifested most prominently though abnormal processing of intensity. The aim of this study is to investigate this in both the auditory and visual domain in children with autism, using both behavioral and neuroimaging methods. Specifically, we will look at intensity dependent processing as a function of varying parameters in both the visual and auditory domains. We have two specific goals for this project. The first is to document in detail any intensity related sensory processing deficits revealed by behavioral and neurological measures in both these sensory domains. We shall study how these deficits vary as a function of elementary stimulus parameters, spectral characteristics in the auditory domain, and contrast and spatial frequency in the visual domain. The second goal is to compare observed impairments across modalities. Behavioral studies will span both magnitude estimation tasks, and forced choice tasks requiring the child to discriminate between stimuli based on intensity. Neuroimaging studies will consist of EEG and MEG imaging of the neuronal responses to the same stimuli. We will look at the growth of magnitude functions resulting from each of these methods, and will attempt to correlate (1) between behavioral and neurological findings (2) between deviation from control data and severity of impairment (verbal or functional). Finally, we hope to gain a deeper insight into the core deficits of autism by looking at primary deficits across modalities.</p>
Preliminary Studies Of The Use Of Digital Video Sampling To Assess Treatment Response In Children With Autism
<p><strong>Bryan H. King, MD, Dartmouth Medical School (Psychometric Award)</strong><br />As controlled clinical trials in children with autism are increasingly performed, an appreciation for the need for better outcomes measures is growing. In part, the difficulty for autism clinical trials derives from the fact that no two children with autism are alike. Further, behavioral problems that are particularly challenging will differ from family to family. Current assessment instruments may be inadequate to capture change that is important to patients and families, and thus recent reports document discordant findings. Investigators see change that parents do not; or parents see change that is lost on investigators. The aims of this project are to explore the utility of obtaining videotaped behavior samples for the assessment of treatment response in children with autism. The proposed studies examine factors that may influence raters, and which may separate parents from investigators with respect to their scoring of behavioral disturbance. This revised and downsized project will provide essential data to inform subsequent large scale studies in which videotaped behavioral samples may be utilized in single and double blind clinical trials. Funded in Partnership with Repligen Corporation</p>
Development of a New Generation of Computer-Implemented Training Tools Designed for Therapeutic Application in Children with Autism Spectrum Disorders
<p><strong>Michael Merzenich, Ph.D., Keck Center for Integrative Neuroscience, UCSF (Genius Award)</strong><br />The primary objective of this research and development project is to design, produce, and test the application of new training tools designed to ameliorate the expressions of autism spectrum disorders (ASD) and to test new strategies designed to prevent the emergence of the full expression of ASD symptoms in at-risk infants. The research is multi-pronged, integrating animal studies of neural plasticity, human behavioral and imaging studies, and testing and development of a new targeted generation of re-training tools for ASD based upon experience with the Fast ForWord programs in ASD subjects.</p><p>First year funding partner: The Autism Coalition for Research and Education</p>
Quantitative Psychophysiologic Evaluation of Sensory Processing in Children with Autism Spectrum Disorders
<p><strong>Lucy Jane Miller, Ph.D., OTR, University of Colorado Health Sciences Center (Psychometrics Award)</strong><br />The proposed study will examine the reliability and validity of an established psychophysiologic assessment of sensory reactivity in 40 school-aged children with Autism Spectrum Disorders (ASD). The quantitative laboratory paradigm, called the Sensory Challenge Protocol has successfully documented sympathetic and parasympathetic nervous system functioning in children with fragile X syndrome, cognitive delays, sensory modulation dysfunction, and ADHD, and field-tested in a group of children with ASD. In this pilot feasibility study (n = 8), the Sensory Challenge Protocol was found to be practicable with ASD, however, a larger scale project evaluating the reliability and validity of the paradigm with children who meet stringent criteria for ASD is needed. The protocol is administered in a non-threatening, fun situation, and 'pretend spaceship during which 50 sensory stimuli are presented while electrodermal reactivity (sympathetic nervous system marker) and vagal tone (parasympathetic nervous system marker) data are collected continuously. The four specific aims are: to evaluate the reliability of the Sensory Challenge Protocol in school-aged children with ASD;to investigate the variability of sensory reactivity among children with ASD;to examine relations among sensory symptoms and core symptoms of autism (e.g., social behaviors, communication, and restricted behaviors); andto evaluate the convergent validity of the laboratory measure with parent-report measures of sensory and functional behaviors.Validation of a quantitative measure of sensory reactivity in children with ASD will further our understanding of individual differences among children with ASD and will be useful in future treatment outcomes research. Funded in Partnership with Repligen Corporation</p>
Immune Phenotypes in Autism Spectrum Disorder
<p><strong>Cynthia A. Molloy, M.D., M.S., Cincinnati Children's Hospital (Pilot Project)</strong><br />Research on the etiology of autism spectrum disorders (ASD) has been hindered by the heterogeneity of the population with this behaviorally defined condition. Previous studies have suggested the possibility that distinct phenotypic subgroups of ASD may be defined, based on history of immune disorders and measurable immune responses. The adaptive immune response involves the proliferation of T helper cells along two divergent, antagonistic lines. The resulting subsets, TH1 and TH2, are distinct immune phenotypes characterized by the particular cytokines they produce and the immune response mediated by those cytokines. The TH1 immune phenotype is associated with organ specific autoimmunity. The TH2 phenotype predominates in an atopic response. Different investigators have reported either TH1 or TH2 predominance in ASD. This molecular epidemiologic pilot study seeks to address this apparent paradox. Our proposed study uses a case control design, comparing children with ASD (cases) to children with other developmental disorders (Control A) and children with neurotypical development (Control B). The specific aims of the study are to 1) compare the histories of atopy and familial autoimmunity between cases and controls, 2) measure peripheral blood cytokines and compare the distribution of TH1 and TH2 phenotypes between cases and controls and 3) examine the relationship between immune phenotype, history of atopy and familial autoimmunity, and the clinical characteristics of ASD. By addressing important methodologic issues such as unbiased selection of cases and controls, and measurement of both medical history and cytokine levels, this study will contribute significant new information about immune phenotypes in ASD.</p>
Social Communication Skills Assessment System for Children with Autism: The ESCS-L and the PICS
<p><strong>Peter Mundy, Ph.D., University of Miami (Psychometrics Award)</strong><br />Research indicates joint attention impairment is pathognomonic of autism, predicts cognitive and social outcomes in these children, and may be an index of neurodevelopmental components of the disorder. Consequently, joint attention has become an important dimension to consider in treatment research. However, current assessment and diagnostic tools lack the efficiency and precision necessary to measure joint attention development in intervention studies. Furthermore, because these skills can be low-frequency, context-specific behaviors in children with autism, the combination of both direct observations and parent or professional report data may be necessary to provide a reliable and valid assessment of this critical domain of social development. To this end we will develop and test the efficacy of the Early Social Communication Scales Live (ESCS-L), a live coding quantitative assessment of social communication skills, and the Pictorial Infant Communication Scale (PICS), a sixteen item measure employing both pictorial and written descriptions of critical behaviors to improve the reliability and validity of informant responses. The psychometric properties of this measurement system will be assessed in an 8-week longitudinal study of 40 children with autism and 20 comparison children. It is expected this research will lead to the development of a system of efficient quantitative measures of a critical domain of social development that will enable researchers to better monitor the growth development and treatment response of children with autism. <strong>Funded in Partnership with Repligen Corporation</strong></p>
Neuroimmune Reactions in the Pathogenesis of Autism
<p><strong>Carlos A. Pardo-Villamizar, M.D., Johns Hopkins University School of Medicine (Pilot Project)<br /></strong>Current evidence suggests that neurobiological abnormalities in autism are associated with changes in cytoarchitectural and neuronal organization that can be determined by genetic, environmental, immunological and toxic factors. Since neuroglia have central roles during brain development for cortical organization, neuronal function and immune responses, we hypothesize that autism is, in part, an immune mediated disorder. In order to determine if neuroimmunological mechanisms contribute to the pathogenesis of autism, we propose to study the profile of neuroglial responses and the presence of cellular and humoral immunopathological reactions, in brain tissues from patients with autism as compared with those from age-matched normal and neurodevelopmental disorders such as Rett's syndrome and Down's syndrome. We also plan to study cytokine pathways involved in neuroinflammation to determine if they have a role in the pathogenesis of autism. These studies may be valuable for the understanding of autism and the design of new therapeutic approaches to treat it.</p>
Characterization of a Mouse Model for Autism
<p><strong>Paul H. Patterson, Ph.D., California Institute of Technology (Pilot Project) <br /></strong>We are developing a mouse model of autism based on epidemiological findings that maternal viral infection can increase the frequency of autism in the offspring. Using a respiratory infection of pregnant mice at E9.5, we find that the offspring display striking behavioral abnormalities in 4 tests relevant to autism. Moreover, these offspring have a deficit in Purkinje cells specifically in lobules VI and VII of the cerebellum, a finding that strikingly parallels the neuropathology in autism. We propose to (i) quantitate and further examine the cerebellar pathology, (ii) using microarray analysis, examine molecular changes in the brains of exposed offspring, at several time points in development and in adulthood, and (iii) investigate the cause of altered fetal brain development, specifically testing the hypothesis that virally-evoked cytokines in the maternal immune response are responsible. The latter experiments will involve the use of cytokine knockout mice, as well as injection of killed virus.</p>
Genotypic and Phenotypic Characterization of Paraoxonase Enzymatic Activity in Autistic Patients and First-degree Relatives
<p><strong>Antonio M. Persico, M.D., University Campus Bio-Medico (Pilot Project)</strong><br />We have recently described an association, to our knowledge replicated in at least two independent studies, between autism and &quot;long&quot; alleles of a polymorphic GGC repeat located in the 5'UTR of the gene encoding Reelin, a pivotal protein for neuronal migration during neurodevelopment. We have also found that long GGC alleles yield reduced protein translation rates, both in vitro and in vivo, and that Reelin exerts a proteolytic activity potently inhibited by organophosphates, compounds routinely used as pesticides and insecticides. Within the framework of a gene-environment interactive model, genetically-vulnerable individuals producing lower amounts of Reelin, if prenatally exposed to organophosphates during critical periods in neurodevelopment, could undergo altered neuronal migration resulting in an autistic syndrome.</p><p>Paraoxonase is the enzyme responsible for detoxification of organophosphates, for hydrolysis of lipid peroxides involved in atherosclerosis and for modulation of cell-mediated immune responses. Impressive 40-fold interindividual differences in serum paraoxonase activity have been documented in humans, largely resulting from functional polymorphisms present in the paraoxonase-1 (PON1) gene, located on chromosome 7q31. The current project is aimed at (a) characterizing paraoxonase enzymatic activity in the serum of autistic patients from A.G.R.E. families; (b) characterizing functional polymorphisms and searching for mutations in the PON1 gene of the same patients, and (c) correlating enzymatic activity and genotypic information to verify whether PON1 polymorphisms/mutations may yield reduced levels of paraoxonase activity, thereby increasing the risk for developmental teratogenesis following prenatal exposure to organophosphates and explaining the enhanced cell-mediated immune responses previously described in many autistic patients.</p><p><strong>Jonathan Pettegrew Memorial Young Investigator Award 2003:</strong></p>
Language Related Working Memory and Executive Functions in Relatives of Individuals with Autism
<p><strong>Abraham Reichenberg, Ph.D., Mount Sinai School Medicine (Young Investigator)</strong><br />Functions of planning, monitoring, inhibition and selective attention are collectively termed: Executive Functions (EF). The term Working Memory (WM) is used generally to refer to a limited-capacity system allowing the temporary storage and manipulation of information in complex cognitive tasks. WM and EF have been suggested as potential endophenotypes for autism. Speech abnormalities have also been characterized as a potential phenotype, and have generated promising genetic findings. Baddeley and Hitch (1974) proposed a four-component WM model that provides a conceptual framework for the central role of temporary storage of information in the development and performance of more complex cognitive tasks, including language acquisition, and Executive Functions. The proposed project will study the familiality of the language-associated components of this well characterized model of WM. In addition, the role of the supervisory component of the model in EF will also be investigated. Given the recent evidence for autism related genes specifically found among families in which the autistic members or their relatives have language deficits, this may be critical for understanding the core deficits in autism.Our hypothesis is that deficits in the language-associated components of the working memory model and the supervisory component will be more frequent among family members of autism probands than among family members of probands with ADHD or family members of normally developing children. Our secondary hypothesis is that EF measures will be directly associated with measures in the supervisory component, and indirectly (i.e., through the measures of the supervisory) with measures in the language-associated components.</p>
Identification of Genes Involved in Autism Using a Drosophila UBE3A Misexpression System
<p><strong>Lawrence T. Reiter, Ph.D., University of California, San Diego (Young Investigator)</strong><br />Loss-of-function of the UBE3A ubiquitin ligase in selected regions of the brain causes the severe mental retardation disorder Angelman syndrome, while elevated expression of this same gene has been strongly implicated autism. One phenotype of autism is a reduced ability to form long term memory. A critical step in understanding the mechanism by which altered levels of UBE3A lead to abnormal brain development or function is to identify the protein targets which are normally degraded by UBE3A dependent ubiquination. We propose to identify UBE3A candidate target proteins using the model system Drosophila melanogaster, which has a single highly conserved homologue of UBE3A. We will employ two complementary strategies to identify such UBE3A targets. First, we will search for genes in flies that alter the phenotypes of flies having reduced or elevated UBE3A activity. Second, we will identify Drosophila proteins that are down-regulated as a consequence of overexpressing human UBE3A in Drosophila. We will then assay for the function of these proteins in well established Drosophila assays for long term memory. The ultimate goal of these studies will be to determine whether human homologues of Drosophila UBE3A targets we identify are misregulated in autism and/or Angelman syndrome.</p>
Planum Temporale and Language in Parents of Children with Autism
<p><strong>Donald C. Rojas, Ph.D., University of Colorado Health Sciences Center (Pilot Project)</strong><br />The main goal of this proposal is to evaluate whether left hemisphere planum temporale (PT) volume reduction, assessed by morphometric analysis of magnetic resonance imaging (MRI) data, is present in the parents of children with autism. Such a finding would bolster support our hypothesis that PT volume reduction represents a familial risk factor for language delay and deviance often seen in individuals with autistic disorder. Preliminary evidence from our laboratory suggests that alteration in the volume of the planum temporale in both adults and children with autism. The planum temporale (PT) is an auditory processing brain region intimately associated with language processing in the left hemisphere in normal development. Measuring the PT in non-affected family members will allow us to assess whether the PT alteration in autism is familial, the next logical step in determining if PT volume change will be a productive endophenotype. We are proposing to measure PT volume and surface area in 20 parents of children with autism, 20 age-matched adults with autism and 20 adults with no personal or familial history of autism or other developmental disorders. We hypothesize that the volume of the left PT will be significantly smaller in the parent group compared to the controls, and that the PT volume in the adult autism group will be lower than that for the parent group (consistent with the view that not all of the parents in the autism group will carry the risk factor in question). We will also measure language function and assess the family history of language development in the same three groups of adults. Measures of receptive and expressive language, as well as phonology and pragmatics, will be obtained in all of the adults and correlated to the MRI findings.</p>
A Population Genetic Study of Autism in a Founder Population
<p><strong>Andres Ruiz-Linares, Ph.D., University College London (Pilot Project)</strong> <br />Autism is perhaps the most heritable of psychiatric disorders and has an estimated prevalence of 1/1000, making this condition a very important public health issue. To date there have been 7 genome-wide searches for autism susceptibility loci. These genome screens have suggested linkage to several regions, particularly on chromosomes 7 and 2. However, these candidate regions are very large and no gene conferring susceptibility to autism has yet been identified. In order to take these encouraging results forward it is essential to examine independent well-characterized study samples. A powerful complement to linkage analysis is the use of linkage disequilibrium mapping in population samples, particularly when drawn from genetically isolated areas. Here we propose to initiate a program of research aimed at identifying autism loci by studying unrelated patients from the founder population of Antioquia, in North West Colombia. We propose to collect a study sample of at least 100 carefully diagnosed autistic patients. The refined clinical assessments aim at enabling the analysis of genetic effects underlying specific autistic symptoms. We will subsequently employ this study sample in whole-genome screens so as to perform linkage disequilibrium mapping of autism loci. The diagnostic assessments that we will carry out in Antioquia are the same being employed in a parallel study of patients from the Central Valley of Costa Rica, a population genetically very similar to Antioquia. The standardization of clinical criteria across studies will facilitate the comparison of genetic mapping results and allow joint analyses of the data. The collaborative study of autism in two closely related population isolates should dramatically increase the power and resolution of the genetic analyse.</p>
Feature Processing in Autism
<p><strong>Sara Jane Webb, Ph.D., University of Washington (Young Investigator)</strong><br />Autism is characterized by impairments in social functioning, communication, and a restricted range of activities. Specific deficits in complex information processing have been proposed as both core and broader phenotype autism deficits (e.g. Frith, 1989; Minshew et al., 1997). The weak &quot;central coherence&quot; hypothesis has focused on the manner in which individuals with autism process complex items. Brock et al. (2002) suggest that weak central coherence reflects a failure of feature binding, which can be indexed by EEG recordings of neural activity in the gamma band range (30 to 80 Hz). The primary goal of this proposal is to explore the relation between gamma activation, a neural index of feature binding, and neurocognitive functioning, in order to better define information processing deficits in individuals with autism. The following questions will be addressed: Are deficits in feature binding, as reflected in gamma band abnormalities, evident in individuals with autism? If so, are they evident across a wide range of stimuli, suggesting a global perceptual processing impairment? Or are these deficits more evident during tasks that involve social processing such as the perception of a face? If such deficits are present, are they correlated with performance on (1) central coherence tasks, and (2) tasks that are known to tap brain regions involved in feature binding (i.e. hippocampus)? This study will help better define the nature of information processing impairments in autism and their neural bases, and provide potentially useful information for genetic studies of broader phenotype.</p>
Investigating Shared Liability to Autism and Related Language Disorders
<p><strong>Lonnie Zwaigenbaum, M.D., McMaster University (Pilot Project)</strong><br />The objectives of this project are 1) to identify families co-segregating autism and language impairments, and to determine the specific domains of language function that are involved, and 2) To localize genes underlying shared liability to autism and language impairments in extended families. Evidence from family and genetic studies of autism suggests that language impairments in relatives result from the same susceptibility genes as autism itself, but likely involve fewer genes and less heterogeneity, which may result in greater power to localize these genes. From among families participating in an ongoing genetic study of autism, we have identified 30 families that include at least 2 autistic probands, and at least 2 relatives screening positive for language impairments. Relatives from these families will be assessed using a battery of measures covering domains of language functioning hypothesized to be genetically related to autism. Language measures which show familial aggregation will be used to define categorical and quantitative phenotypes, which will then be studied using linkage analysis to localize underlying genes. We will use non-parametric analyses, which are applicable to both categorical and continuous traits and do not require the specification of genetic transmission parameters. For categorical phenotypes (e.g., presence/absence of speech delay), we will test for excess allele sharing among sets of affected relatives, with non-parametric linkage (NPL) scores computed with the program ALLEGRO. Significant linkage will be declared when the observed NPL score exceeds 4.4 (p-value&lt; 2.5x10-5) to ensure a genomewide type I error of 0.05. Quantitative traits will be localized using multipoint variance component linkage methods.</p><p>First year funding partner: The Autism Coalition for Research and Education</p>
ScienceAbraham ReichenbergAHM Mahbubul HuqAndres Ruiz-LAntonio M. PersicoBryan H. KingCalifornia Institute of TechnologyCarlos A. Pardo-VillamizarCincinnati Children's HospitalCynthia A. MolloyDartmouth Medical SchoolDonald C. RojasElizabeth a. HoffmanGeorgetown University Medical SchoolJohns Hopkins University School of Medicine (Pilot Project)Jonathan Pettegrew Memorial Young Investigator Award 2003Keck Center for Integrative NeuroscienceLawrence T. ReiterLucy Jane MillerM.S.Michael MerzenichMount Sinai School Medicine (Young Investigator)OTRPasteur InstitutePaul H. PattersonPeter MundyPh. D.Ph.D.San DiegoSan FranciscoTal KenetThomas BourgeronUCSFUniversity Campus Bio-MedicoUniversity of CaliforniaUniversity of Colorado Health Sciences CenterUniversity of MiamiWayne State UniversityGrantsGrantsWed, 04 May 2011 23:14:29 +0000pwhalen@gmail.com414 at https://www.autismspeaks.org2004 Grants Funded (CAN) https://www.autismspeaks.org/science/grants-program/research-we-have-funded/2004-grants-funded-can
Molecular Studies in Autism
<p><strong>Huda Zoghbi, M.D., Baylor College of Medicine (Genius Award)</strong><br />The funds received through the Cure Autism Now Genius Award will allow us to explore new approaches to identify some of the molecular genetic pathways involved in autism. Our strategy will focus on the following hypothesis: Genes that are key in mediating prominent phenotypes seen in autistic patients are likely to be mutated, at least, in a subset of autism patients. A two-pronged approach will be taken to hone in on the most promising candidate pathways.</p>
Oxidative Stress in Autism
<p><strong>Xue Ming, M.D., Ph.D., UMDNJ-New Jersey Medical School (Pilot Project)</strong><br />Autism is caused by the interaction of genetic and environmental factors. One of the best understood causes of autism is fetal exposure to thalidomide. Thalidomide causes fetal malformation in rabbits by a mechanism involving oxidative stress. Our hypothesis is that a similar mechanism occurs in human autism cases. Oxidative stress could also be involved in the common form of human autism unrelated to thalidomide. Many common environmental toxins can induce oxidative stress in genetically susceptible hosts. Genetic susceptibility factors for autism could include common polymorphic variants of enzymes that normally protect against oxidative stress.</p><p>We will test our hypothesis by determining whether individuals with autism have elevated levels of oxidative stress biomarkers in urine and decreased levels of anti-oxidant enzymes in plasma and erythrocytes. We will also test whether the frequency of common polymorphisms of the antioxidant enzyme glutathione peroxidase 1 is altered in autism trios by the transmission/disequilibrium test. We expect to document that reactive oxygen species and oxidative stress mechanisms play an important role in autism, the findings that could lead to new approaches to prevention and treatment of the disorder.</p>
Studies of Neuropeptide and Protease Patterns of Autistic Children to Elucidate Pathophysiological Mechanisms, Facilitate Diagnostics and Allow New Types of Treatment
<p><strong>Andres Grubb, M.D., Ph.D., Lund University Hospital Sweden (Treatment Award)</strong><br />The pathophysiology of autism involves abnormal communication between neurons, probably associated with abnormal patterns of neuropeptides in the brain. Abnormal levels of neuropeptides might be revealed by proteomic studies of proteins/peptides below 10 kDa in spinal fluid and/or blood plasma. Detection of abnormal levels of peptides in autism will allow generation of new hypotheses concerning its patho-physiology and might facilitate diagnostics and suggest new treatment possibilities. Since most neuropeptides are generated by proteolysis of larger precursor molecules abnormal levels of neuropeptides might be caused by abnormal proteolytic activity.</p><p>We have plasma and spinal fluid samples from 20 autistic and 20 control children and a preliminary SELDI-TOF system for studying proteins/peptides below 10 kDa. We have used this system to investigate 4 autistic and 4 control children and have detected two peptides that display uniquely high concentrations in autism.</p><p>We plan to collect samples from more than 40 autistic and control children, elaborate the SELDI-TOF system to allow study of at least 200 proteins/peptides below 10 kDa and use this system to detect peptides of uniquely low or high concentration in autism.</p><p>We also plan to structurally characterize those two autism-related peptides already identified, as well as those our further research will identify.</p><p>We will also directly analyze arginine-vasopressin, oxytocin, prolactin, neurotensin, substance P, TRH, neuropeptide Y and angiotensin in autistic and control children and study the activity of those proteolytic enzymes that might be involved in the metabolism of the (neuro-)peptides that display abnormal concentrations in autism.</p>
Reading and Writing Program for visual Learners
<p><strong>O. Ivar Lovaas, Ph. D., University of California, Los Angeles (Treatment Award)<br />Research Partner: Chaka Khan Foundation in support of Tallon's Tower<br /></strong>It has long been suspected that the autistic child's failure to develop language may constitute a significant factor in the etiology of autism. The proposed research intends to test the effectiveness of a newly developed Reading and Writing (R&amp;W) Program with young autistic children who are delayed in the acquisition of vocal language. Teaching these children to read and write will allow them to communicate more effectively with parents and caregivers, leading to a better quality of life as well as treatment outcome. A single-case experimental design, multiple baseline across participants, will be implemented in order to determine the effectiveness of the R&amp;W Program. Treatment begins with 6 months of intensive 1:1 behavioral intervention, 40 hrs/week, where the Vocal Language Program will comprise 30 hrs/week of treatment. At the end of 6 months, children will be divided into two groups: visual and vocal learners, based on ability to imitate vocal behavior. Vocal learners will proceed with the standard vocal language program, while visual learners (i.e., non-vocal children) will be assigned to a baseline condition lasting 1 month, 3 months, or 5 months, during which time they will continue receiving vocal language training. During the 6-month treatment phase, participants will receive 15 hrs/week of training in both the Vocal Language Program and the R&amp;W Program. The proposed study will focus on the R&amp;W Program's effect on rates of language acquisition (including facilitation of vocal language) and participants' affect.</p>
Prevention of Autism Spectrum Disorders by Modulating T Cell Responsiveness
<p><strong>David A. Ostrov, Ph.D., University of Florida-College of Medicine (Treatment Award)<br /></strong>Autism is a behaviorally defined developmental disability manifesting in early childhood and affecting approximately 3 in 500 individuals in the United States. Many autistic subjects exhibit immune imbalances in lymphocyte populations and gastrointestinal immunopathology. There is a strong genetic component to autism spectrum disorders, as concordance is observed in 75% of identical twins. Complex interactions between genetic and environmental factors are thought to contribute to autism susceptibility. Several key autism susceptibility loci have been recently described including the HLA-DRB1 gene in the major histocompatibility complex (MHC) class II region on chromosome 6p21. Although a significant proportion of the inherited predisposition to autism maps to the class II region of the MHC, the mechanisms for how these genes influence the initiation of abnormalities in neurological development are not clear. Evidence exists to suggest that class II MHC DR molecules bind self and/or environmental antigens that may trigger T cells capable of recognizing components of the developing nervous system. This proposal aims to prevent autism by building on two recent significant advances in the field: 1) the discovery of genetic linkage between autism and the MHC, and 2) determining the complete sequence of the MHC. The complete sequence of he MHC reveals the full extent of genes in this region that influence susceptibility to autism spectrum disorders. The objective of the proposed study is to establish a method to prevent autism by modulation the function of MHC encoded proteins using structure-based strategies.</p>
Vagus Nerve Stimulation and the Control of Social and Exploratory Behavioral Deficits in a Rodent Model of Autism
<p><strong>Benjamin R. Walker, Ph. D., Georgetown University (Treatment Award)</strong><br />In an effort to identify and control the neural substrates mediating the altered social and exploratory behavior see in autism, this proposal aims to evaluate the role of brainstem nuclei in the regulation of behavioral alterations caused by developmental cerebellar injuries. Previously we demonstrated that focal inhibition in the medial nucleus of the solitary tract (mNTS), the primary target of afferent vagal fibers, and the lateral parabrachial nucleus (lPBn), an important pontine relay station for ascending projections from the NTS, attenuated limbic motor seizures evoked from the forebrain. In the present proposal, we test the hypotheses that similar inhibition of these brainstem nuclei, via decreases in glutamate or increases in GABA activation, can amiliorate social and exploratory behavior deficits. To this end, we focally applied the GABA agonist muscimol (256 pmol) or the glutamate antagonist kynurenate (634 pmol) into the NTS in control rats and rats with specific developmental lesions to the climbing fibers of the inferior olive nucleus from postnatal exposure to 3-acetylpyridine (85 mg/kg) or mechanical cerebellar damage while recording their social behavior. Preliminary results demonstrate that alterations in glutamate and GABA neurotransmission within the brainstem and pons is capable of lessening the detrimental effects of cerebellar damage in a rodent model of autism. These results suggest that autistic and seizure behaviors may involve similar neural substrates, and that new treatments for seizures, such as vagal nerve stimulation, which alter these pathways may be effective for treating autism.</p>
Smith-Lemli-Opitz Syndrome (SLOS)_and Children with Autism.
<p><strong>Elaine Tierney, M.D., Kennedy Kreiger Institute (Bridge Award)<br /></strong>The investigators seek to determine the incidence of Smith-Lemli-Opitz Syndrome (SLOS) in a cohort of subjects with autism spectrum disorders (ASD) in multiplex families. SLOS is a disorder of cholesterol metabolism that has been found to be associated with autism [Tierney et al., 2000]. In a study of subjects with SLOS [Tierney et al., 2001], it was found that of 17 subjects administered the ADI-R algorithm questions, 9 (53%) met the Autism Diagnostic Interview- Revised (ADI-R) [Lord et al, 1993; Lord et al., 1994] criteria for autism (the algorithm questions but not the complete ADI-R was administered).</p><p>The incidence of SLOS among individuals with ASD is unknown. The knowledge of the percentage of individuals in a cohort of multiplex families who have ASD will help the medical community to know which subjects with ASD should have serum testing for SLOS.</p><p>The authors propose to test 29 AGRE serum samples from subjects born into multiplex families with ASD for biochemical evidence of SLOS. If any subjects with ASD are found by serum testing to have SLOS, the AGRE database will contact the families and the investigators will then work with the families (if the families wish to contact the investigators) to ensure that they are referred for appropriate medical care, including dietary cholesterol supplementation.<br /></p>
White Matter/Brain development Initiative
<p><strong>Martha Herbert, M.D., Ph.D., Massachusetts General Hospital (Innovator Award)<br /></strong>This project will pursue a suggestive and provocative finding about the brain in autism, namely that we see enlarged superficial, or radiate, white matter in the brains of autistic individuals. White matter is the part of the brain containing the axons or &quot;wires&quot; that connect neurons in different regions to one another; it is white because of the lipid insulation, called myelin, that surrounds each axon. Dr. Herbert's identification of the radiate zone (right under the cerebral cortex, the gray matter where cortical neurons live) as the part of the white matter contributing most to making many autistic brains unusually large is provocative because it gives suggestive leads for further research on many levels at once: timing (something is manifesting postnatally, as we already knew from the fact that head size gets larger after birth), the nature of tissue changes (related to white matter), mechanism (something that affects regulation of white matter development after birth), and functional impact (possible altered connection among regions, that may impair information processing and lead to abnormal behaviors). This project will therefore develop a collaborative research program, because we need coordinated cooperation across disciplines to explain this brain change in an integrative fashion. The project will also expand upon this research effort to develop comprehensive models of autism. Models that integrate the multiple levels of research about autism are much needed to strengthen and speed up our efforts to understand, diagnose, treat and prevent autism.<br /><strong>Research Partners: The Autism Coalition for Research and Education (ACRE) and Daniel and Carol Tyukody, Jr.</strong></p>
GeneWays Project
<p><strong>Andrey Rzhetsky, Ph.D., Columbia University (Innovator Award)</strong><br />We wish to conduct a two-pronged analysis of autism (as a biological process or a developmental disturbance), making use of the rich information accumulated in several unrelated fields. We will compile information about molecular interactions in human neurons using our unique text-mining facilities (in the GeneWays system), and we will examine a wide spectrum of disorders with which autism shows non-random association (neurological, autoimmune, epidermal, and many other groups of disorders that have a strong hereditary component). Through this joint analysis, we will compile a computational regulatory model of autism. We also hope to list candidate genes by the probability that they harbor genetic polymorphisms that affect the bearer's susceptibility to developing symptoms of autism.</p>
Accurate GSR measurements for people with autism
<p><strong>Dov Sagi, Ph.D. and Yoram Bonneh, Ph.D. Weizmann Institute of Science, Israel (Bridge Award)</strong><br />The GSR (Galvanic Skin Response) is a potentially useful measure of the level of arousal in people with autism, especially in relation to external or self generated stimulation. This has been demonstrated in two studies, which found abnormal autonomic response in autistic children. The use of GSR could potentially help with many behavioral and educational issues, such as providing the teacher/parent with a simple feedback method to monitor arousal of the child, or it could be used to alert teacher/parent of changes in arousal that might signal the onset of episodes of aggression, or other serious out of control behaviors, allowing the teacher/parent to intervene pro-actively and possibly avert the episode. One major difficulty in using GSR for autism is the need to attach a wired device to the body, which most autistic children do not like. Moreover, typical self-stimulation could alter the GSR signal by the movement of the hands. Our purpose is to explore the potential use of recently developed GSR devices, which are wireless and claimed to be more accurate. This preliminary exploration could lead to further and more elaborate studies in the future.</p>
Neural and Behavioral Correlates of Visual Integration and Visual Search Processing in Autism. A Probe for Early Assessment.
<p><strong>Giovanni Cioni, M. D., Stella Maris Scientific Institute &amp; University of Pisa, Italy (Treatment Grant)</strong><br />Autism has been considered for decades to be a developmental disorder based on social and communicative impairment. More recently, the possibility of perceptual and sensorial deficits in autism has been considered to be a contingent cause and possible explanation of this disorder. Both ecological observations and systematic studies of autistic subjects have found general abnormalities of perceptual abilities. In particular, there seems to be an imbalance between the processing of local vs. global visual information (e.g. Jolliffe &amp; Baron-Cohen, 1997; Plaisted, O'Riordan &amp; Baron-Cohen, 1998; Mottron, Belleville &amp; Menard, 1999). The goal of this study is to explore the visual cortical processing in autism using Visual Evoked Potential (VEP) and the perceptual processes using psychophysical techniques and eye movement recording. Our aim is to understand how local signals are integrated across space to generate global percepts and visually guided behavior in autism. The identification of the neural substrate underlying these perceptual computations is crucial, because it may represent the neural substrates for feature grouping and figure-ground segregation and because developmental deficits in a common processing architecture may have wider effects on cognitive development. The results of this study may provide fundamental basic knowledge to re-interpret some theories of autism. In fact, it may add knowledge on the early perceptual stages of the cognitive system, providing essential constraints to any middle- and high-level cognitive theory of autism. Moreover, the electrophysiological techniques we will develop may provide a new set of tools for early diagnosis of autism in infancy and early childhood.</p>
Early Identification of Infants and Toddlers at Risk for Autistic Spectrum Disorder (ASD)
<p><strong>Carole Samango-Sprouse,Ed.D, Neurodevelopmental Diagnostic Center for Young Children, Inc. (Bridge Grant)</strong><br />The proposal study will investigate a quick, efficient and reasonable method to identify infants at risk for ASD. It will increase the health care providers vigilance of a serious disorder and could lead to earlier identification and treatment for ASD.</p>
Otoacoustic Emission Testing of Children with Autism Spectrum Disorders
ScienceAndres GrubbAndrey RzhetskyBaylor College of MedicineBenjamin R. WalkerCarole Samango-SprouseColumbia UniversityDavid A. OstrovDov SagiEd.DElaine TierneyGeorgetown UniversityGiovanni CioniHuda ZoghbiInc.IsraelItalyKennedy Kreiger InstituteLos AngelesLund University Hospital SwedenMartha HerbertMassachusetts General HospitalNeurodevelopmental Diagnostic Center for Young ChildrenO. Ivar LovaasPh. D.Ph.D.Ph.D. and Yoram BonnehPh.D. Weizmann Institute of ScienceStella Maris Scientific Institute & University of PisaUMDNJ-New Jersey Medical SchoolUniversity of CaliforniaUniversity of Florida-College of MedicineXue MingGrantsGrantsWed, 04 May 2011 22:15:29 +0000pwhalen@gmail.com413 at https://www.autismspeaks.org